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Showing papers in "International Journal of Cancer in 1974"


Journal ArticleDOI
TL;DR: Human wart virus was isolated from plantar warts and component I was transcribed into radioactive complementary RNA (cRNA) with the aid of Escherichia coli RNA polymerase, and used as a probe for the detection of wart viral DNA in human warts, condylomata acuminata, laryngeal papillomas and some malignant human tumors.
Abstract: Human wart virus was isolated from plantar warts. After extraction of its DNA, component I was transcribed into radioactive complementary RNA (cRNA) with the aid of Escherichia coli RNA polymerase. The resulting cRNA annealed specifically to wart viral DNA and was used as a probe for the detection of wart viral DNA in human warts, condylomata acuminata, laryngeal papillomas and some malignant human tumors. High concentrations of hybridizing DNA were found in plantar warts. Verrucae vulgares annealed to a considerably lower extent only, indicating that very few genome equivalents were present in those papilloma cells. Some verrucae vulgares were found to be completely negative in this test. Condylomata acuminata, as well as laryngeal papillomas and all malignant tumors tested, did not hybridize with wart viral cRNA.

256 citations


Journal ArticleDOI
TL;DR: It is concluded that the virus does not really travel along with malignant lymphomas as a passenger in the seropositive patients, and the EBNA antigen test appears a relatively simple way of testing for the presence of the virus genome, provided it is carried out with appropriate controls.
Abstract: Twenty-six of 27 African Burkitt lymphomas with histologically confirmed diagnosis contained relatively large amounts of EBV DNA (10–101 viral genomes per cell), as determined by nucleic acid hybridization. Twenty-five of the 26 EBV DNA-positive lymphomas contained the EBV-determined nuclear antigen, EBNA, in the majority of the nuclei. Technical reasons may have accounted for the apparent EBNA-negativity of one EBV DNA-positive biopsy. Four African lymphoma biopsies, one with a definite diagnosis of Burkitt's lymphoma and three with a questionable diagnosis of the same disease, were all EBV DNA- and EBNA-negative. The same was true for a collection of Swedish cases of Hodgkin's disease, lymphocytic lymphoma, chronic lymphatic leukemia and some other lymphoproliferative malignancies. Thus, there is excellent agreement between the presence of EBV DNA and of EBNA in tumor biopsies. The EBNA antigen test therefore appears a relatively simple way of testing for the presence of the virus genome, provided it is carried out with appropriate controls. Several of the EBV-genome and EBNA-negative cases came from patients with high serum titers of EBV antibodies. It is concluded that the virus does not really travel along with malignant lymphomas as a passenger in the seropositive patients. In comparison with other lymphomas, African Burkitt's lymphoma of the high endemic areas is unique in that the tumors (with rare exceptions) represent the proliferation of an EBV-genome carrying clone. These findings stress the necessity to distinguish between EBV-seropositive status and evidence for EBV-genome-carrying neoplastic cells.

256 citations


Journal ArticleDOI
TL;DR: It is suggested that cell‐mediated mutagenesis with human cells should provide a useful system to test for environmental chemicals hazardous to humans that have to be metabolically activated.
Abstract: Chemically non-reactive carcinogens, such as polycyclic hydrocarbons, have to be metabolized by cellular enzymes in order to exert their biological effects including mutagenicity. Chinese hamster V79 cells can be efficiently mutated from 8-azaguanine susceptibility to resistance by N-methyl-N-nitro-N-nitrosoguanidine. But these cells do not metabolize polycyclic hydrocarbons and were therefore not mutated by these compounds. A system of cell-mediated mutagenesis with carcinogenic hydrocarbons has been developed, by co-cultivating V79 cells with lethally irradiated rodent cells that can metabolize the carcinogens. The number of mutations was dependent on the number of metabolizing cells and the carcinogens were not mutagenic when V79 cells were co-cultivated with non-metabolizing cells. Inhibition of the hydrocarbon metabolizing enzymes by 7,8-benzoflavone, inhibited mutagenicity. Cell-mediated mutagenicity was obtained with the carcinogenic hydrocarbons 7,12-dimethylbenz (a)anthracene, benzo(a)pyrene and 3-methylcholanthrene and there was no mutagenicity with the non-carcinogenic hydrocarbon benz(a)anthracene. The degree of mutagenicity was related to the degree of carcinogenicity and the method detected mutagenicity with 0.1μg/ml. It is suggested that cell-mediated mutagenesis with human cells should provide a useful system to test for environmental chemicals hazardous to humans that have to be metabolically activated. Mutagenese des Cellules de Mammiferes Induite par des Carcinogenes Chimiques Avec Mediation Cellulaire Les carcinogenes chimiquement non reactifs, tels que les hydrocarbures polycycliques, dovent etre metabolises par des enzymes cellulaires afin d'exercer leurs effets biologiques, notamment la mutagenicite. Des cellules V79 de hamster chinois peuvent etre efficacement mutees par la N-methyl-N-nitro-N-nitrosoguanidine et devenir resistantes a la 8-aza-guanine alors qu'elles y etaient sensibles. Mais ces cellules ne metabolisent pas les hydrocarbures polycycliques et ne sont donc pas mutees par ces composes. Un systeme de mutagenese a mediation cellulaire par les hydrocarbures carcinogenes a ete mis au point par co-culture de cellules V79 avec des cellules de hamster pouvant metaboliser les carcinogenes. Le nombre de mutations depend du nombre de cellules metabolisantes et les carcinogenes ne sont pas mutagenes lorsque les cellules V79 sont co-cultivees avec des cellules non metabolisantes. L'inhiition des enzymes metabolisant les hydrocarbures pa la 7,8-benzoflavone empeche la mutagenicite. La mutagenicite a mediation cellulaire a ete obtenue avec les hydrocarbures carcinogenes 7,12-dimethylbenz (a) anthracene, benz (a) pyrene et 3-methylcholanthrene, mais pas avec le benz (a) anthracene qui n'est pas carcinogene. Le degre de mutagenicite etait lie au degre de carcinogenicite. Les auteurs astiment que la mutagenese par l'intermediaire de cellules humaines devrait fournir un bon systeme pour tester les produits chimiques de l'environnement qui sont dangereux pour l'homme et qui doivent etre actives metaboliquement.

237 citations


Journal ArticleDOI
TL;DR: The transformation‐associated change in the quantity of the SF molecule supports the proposal that tissue‐specific surface glycoproteins, such as the SF antigen, express the stage of differentiation at the membrane of normal cells and may be involved in intercellular control of growth and movement.
Abstract: Normal chick fibroblasts are known to contain a tissue-specific surface component, a major glycoprotein (SF) antigen that is also present in chicken serum This antigen was greatly reduced in amount or absent in fibroblasts transformed by five different Rous sarcoma virus strains Fibroblasts infected with virus mutants temperature sensitive for transformation recovered the SF antigen when maintained at the non-permissive temperature Productive infection with a non-transforming avian type-C virus did not alter the level of SF antigen characteristic of normal fibroblasts Polyacrylamide gel electrophoresis of total cell extracts indicated that proteins with apparent mol wt of 145,000 and mol wt 210,000 were greatly decreased following transformation of the fibroblasts That the ability to synthetize the 145,000 mol wt polypeptide was lost upon transformation was implied by pulse labelling experiments, in which normal fibroblasts incorporate [35S] methionine into the above polypeptide whereas transformed cells lose this ability This polypeptide, unique in its presence in normal but not in transformed cells, appears to have an exceptionally high rate of turnover Indirect evidence suggests that the 145,000 and 210,000 polypeptides are molecular counterparts of the SF antigen The transformation-associated change in the quantity of the SF molecule supports our proposal that tissue-specific surface glycoproteins, such as the SF antigen, express the stage of differentiation at the membrane of normal cells and may be involved in intercellular control of growth and movement

212 citations


Journal ArticleDOI
TL;DR: There was a pronounced effect of body weight and height on breast cancer risk; the significance of this in explaining international differences in incidence is stressed.
Abstract: A prospective study of breast-cancer risk in postmenopausal women has been carried out with the cooperation of 50 general practitioners. A total of 7,259 women have been followed up for an average period of 5.4 years (maximum 8.1 years); 70 cases of breast cancer occurred. The main finding was a pronounced effect of body weight and height on breast cancer risk; the significance of this in explaining international differences in incidence is stressed. High parity counteracted the risk of high weight regarding breastcancer. Single women did not show a high risk because of their relatively low body weight. The relative risk in women with a previous mastectomy was five-fold.

202 citations


Journal ArticleDOI
TL;DR: The results confirm and extend previous reports that the carcinoma cells harbor EBV genomes and are confirmed to be free of antibodies to other nuclear antigens.
Abstract: Fresh nasopharyngeal carcinoma (NPC) biopsies were treated in several ways to yield satisfactory cell preparations for detection of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) by anti-complement immunofluorescence tests. If the cells were well dispersed (trypsinization or extensive mechanical dispersal) few or none of them were EBNA-positive. In contrast, if the biopsy preparations contained small to moderately sized tissue fragments (touch preparations or limited mechanical dispersal), nuclear staining was detected in nearly every cell at the margin of the fragments or in cell sheets protruding from them. The stained cells corresponded to the carcinoma cells when compared to histologically stained replicate cell preparations. Nuclear staining was obtaining with anti-EBNA positive sera [healthy donors, NPC patients, convalescents from infectious mononucleosis (IM)], shown to be free of antibodies to other nuclear antigens, but not with anti-EBNA negative sera (healthy donors or patients in the early acute phase of IM). These results confirm and extend previous reports that the carcinoma cells harbor EBV genomes. The implications of these findings are discussed.

158 citations


Journal ArticleDOI
TL;DR: The presented morphological and functional characteristics closely resemble those of lymphosarcoma cells in short‐term culture and distinguish both lines from Epstein‐Barr virus‐carrying lymphoblastoid lines obtainable from normal and malignant lymphoid tissue.
Abstract: Two human cell lines, U-698 M and U-715 M, with unique characteristics were derived from two patients with lymphosarcoma. The presented morphological and functional characteristics closely resemble those of lymphosarcoma cells in short-term culture and also distinguish both lines from Epstein-Barr virus-carrying lymphoblastoid lines obtainable from normal and malignant lymphoid tissue. It is therefore proposed that the lines originate from the donors' tumor-cell population.

154 citations


Journal ArticleDOI
TL;DR: Peritoneal and lung macrophages from CBA mice injected with Corynebacterium parvum tested for in vitro inhibition of growth and DNA synthesis of syngeneic tumour cells inhibited the growth of RI leukaemia cells, and theDNA synthesis of RILeukaemia and T3 fibrosarcoma cells.
Abstract: Peritoneal and lung macrophages from CBA mice injected with Corynebacterium parvum were tested for in vitro inhibition of growth and DNA synthesis of syngeneic tumour cells. Peritoneal macrophages inhibited the growth of RI leukaemia cells, and the DNA synthesis of RI leukaemia and T3 fibrosarcoma cells. Maximum inhibition of DNA synthesis was at 5 days after C. parvum injection. Inhibition was most effective when contact between macrophages and target cells was allowed, since medium from macrophage cultures was only slightly inhibitory. Macrophages maintained alone in culture for 48 h lost their ability to inhibit RI cell DNA synthesis. Lung macrophages inhibited the DNA synthesis of RI cells most effectively 14 days after C. parvum injection.

141 citations


Journal ArticleDOI
TL;DR: This is an expository paper which reviews the rationale for determining prognostic factors and the statistical methods for finding and allowing for such factors in the design and analysis of clinical studies.
Abstract: This is an expository paper which reviews the rationale for determining prognostic factors and the statistical methods for finding and allowing for such factors in the design and analysis of clinical studies The delineation of prognostic factors in clinical studies is useful: in possibly providing insight into the mechanism of disease; in the determination of stratifications of patients for planning clinical trials; in facilitating the comparison between the outcomes of disease in different groups of patients; in assisting in the allocation of treatment to an individual patient and in permitting remedial action A response variable is a measure of the future health or illness of the patient and its value is usually dependent on one or more prognostic variables Statistical methodology for determining prognostic factors is reviewed for the case in which response is dichotomous, continuous or a measure of time (with the possibility of censored observations) and when the predictor variables are discrete or continuous (or a combination of both types) Methods of allowing for known prognostic variables in the analysis of a study are reviewed These include: grouping of patients according to prognostic variables and comparing treatments separately within each group; covariance analysis and maximum likelihood Knowledge of prognostic factors is useful in defining a control group which is to be compared with a treated group in non-randomized studies Three examples of studies designed to elucidate prognostic factors are described, one each in breast cancer, cancer of the prostate and Hodgkin's disease Methodes Statistiques D'Identification et D'Utilisation des Facteurs de Pronostic Le present expose analyse la facon de determiner les facteurs de pronostic et les methodes statistiques utilisees pour definir et appliquer ces facteurs dans la conception et l'analyse des etudes cliniques Il est utile de determiner les facteurs de pronostic pour les etudes cliniques: cela peut donner un apercu du mecanisme de la maladie, permettre de definir les strates de malades en vue de planifier les essais cliniques, faciliter la comparaison entre l'issue des maladies dans divers groupes de sujets, aider a determiner le traitement a appliquer a un malade donne et permettre une action curative Une variable de reponse est une mesure de l'etat de sante ou de maladie futur d'un sujet et sa valeur depend habituellement d'une ou de plusieurs variables de pronostic Les methodes statistiques de determination des facteurs de pronostic sont analysees ici pour les cas ou la reponse est dichotomique, continue ou limitee dans le temps (avec la possibilite d'observations incompletes) et ou les variables previsionnelles sont discontinues ou continues (ou combinent les deux types) Les methodes d'application des variables de pronostic connues sont egalement etudiees dans le present article Elles comprennent: la classification des malades selon les variables de pronostic et la comparaison des traitements dans chaque groupe, l'analyse de la covariance et la probabilite maximale La connaissance des facteurs de pronostic permet de definir un groupe temoin qui sera compare au groupe traite dans les etudes non aleatoires Les auteurs donnent trois exemples d'etudes destinees a definir les facteurs de pronostic, l'un pour le cancer du sein, l'autre pour le cancer de la prostate et le troisieme pour la maladie de Hodgkin

136 citations


Journal ArticleDOI
TL;DR: The ability of a malignant tumour to generate local or systemic excess of membrane‐derived antigen may assist successful escape from specific cellular immune destruction, and neuroblastoma‐specific immune complexes produced maximum blocking of autochthonous lymphocytotoxic immunity at antigen‐antibody equivalence.
Abstract: Eight children with neuroblastoma and five with Wilms' tumour, or osteogenic sarcoma, had serum taken at diagnosis (progressor sera) and again several weeks after the start of treatment (remission sera). Progressor sera, which specifically blocked in vitro, lymphocytotoxic immunity for autochthonous tumour cells, contained immune complexes of tumour-specific antigen and antibody. Blocking progressor sera from five patients contained both complexes and free antigen, while maximum blocking activity was found in three progressor sera which contained complexes but neither free antigen nor free antibody. Remission sera contained neuroblastoma-specific antibody which specifically bound antigenic protein spontaneously released from autochthonous tumour-cell membranes in vitro, and also bound soluble antigen in progressor serum. Neuroblastoma-specific immune complexes, formed by titration of autochthonous remission serum and membrane-turnover antigen, produced maximum blocking of autochthonous lymphocytotoxic immunity at antigen-antibody equivalence. Complexes formed in antigen excess showed moderate blocking activity while complexes formed in antibody excess showed minimal blocking activity. The ability of a malignant tumour to generate local or systemic excess of membrane-derived antigen may assist successful escape from specific cellular immune destruction.

122 citations


Journal ArticleDOI
TL;DR: The cytotoxic effects scored with the unfractionated melanoma patients' lymphocytes, which in general were stronger than the effects seen with the corresponding lymphocyte populations from healthy donors, again appeared to be located mainly in the non‐T‐cell populations.
Abstract: Lymphocytes from 25 healthy donors were separated into T- and non-T-fractions by means of E and EAC rosette-formation. The unfractionated lymphocyte population was tested simultaneously with E and non-EAC rosette-forming cells (T-cells) and EAC and non-E rosette-forming cells (non-T cells) on melanoma cells from cell lines and short-term cultures. More frequent and stronger cytotoxic effects were seen on melanoma target cells from cell lines than from short-term cultures. The cytotoxic effects of the unfractionated lymphocyte populations were always recovered in the non-T-cell populations. Occasionally also T-cell cytotoxicity was seen on melanoma cells from cell lutes. Compared to the T-cell effects, the non-T cells always showed stronger cytotoxic effects. Lymphocytes from selected melanoma patients (patients with known cytotoxic lymphocytes) were also tested tegether with lymphocytes from healthy donors. The cytotoxic effects scored with the unfractionated melanoma patients' lymphocytes, which in general were stronger than the effects seen with the corresponding lymphocyte populations from healthy donors, again appeared to be located mainly in the non-T-cell populations.

Journal ArticleDOI
TL;DR: The significance of the abnormality as an indication of cells transformed by the virus in vivo is discussed, and the importance of this considered in relation to a possible oncogenic role for EB virus in man is considered.
Abstract: The occurrence and incidence of a characteristic banding abnormality in a No. 14 chromosome has been studied in Burkitt-lymphoma-derived and certain other EB virus-associated lymphoblastoid cell lines. The abnormality was readily detected in 7 out of 7 Burkitt lines, and when present could be seen in 100% of cells with recognizable No. 14 chromosomes. In contrast, the abnormality was not observed in 775 cells from 31 infectious mononucleosis-derived lines nor in 450 cells from 18 lines obtained from cord blood lymphocytes experimentally transformed by EB virus in vitro. The significance of the abnormality as an indication of cells transformed by the virus in vivo is discussed, and the importance of this considered in relation to a possible oncogenic role for EB virus in man.

Journal ArticleDOI
TL;DR: Data show that Epstein‐Barr virus‐specific cRNA annealed significantly with DNA from nasopharyngeal carcinoma biopsies as well as with DNA preparations from leukocytes, bone marrow, lymph node and spleen of some patients with infectious mononucleosis, and that such a relationship (if it exists) must differ quantitatively to a considerable extent from the one observed with EBV in EBV‐associated tumors.
Abstract: DNA derived from various human malignant and non-malignant tissues was hybridized with radioactive complementary RNA (cR NA) synthetized in vitro with the aid of Ecoli-RNA-polymerase by using DNA of human herpes group viruses as templates. Epstein-Barr virus (EB V) -specific c R NA annealed significantly with DNA from nasopharyngeal carcinoma biopsies as well as with DNA preparations from leukocytes, bone marrow, lymph node and spleen of some patients with infectious mononucleosis. No significant hybridization was observed with either herpes simplex type 2 or type I cRNA and DNA from ten cervical carcinoma biopsies. cRNA of human cytomegalovirus and varicellazoster virus did not hybridize with DNA from Kaposi’s sarcoma or DNA from heavily infiltrated spleens of patients with Hodgkin’s disease. These data do not exclude a role of these herpes viruses in the etiology of cervical carcinoma, Kaposi’s sarcoma and Hodgkin’s disease. They show, however, that such a relationship (if it exists) must differ quantitatively to a considerable extent from the one observed with EBV in EBV-associated tumors.

Journal ArticleDOI
TL;DR: The results of two studies which compared the HL‐A profile of predominantly Chinese patients with nasopharyngeal carcinoma to that of suitably chosen controls demonstrated a significant increase in the proportion of NPC patients in whom less than two second locus antigens were detectable.
Abstract: This paper reports the results of two studies which compared the HL-A profile of predominantly Chinese patients with nasopharyngeal carcinoma to that of suitably chosen controls. The first study demonstrated a significant increase in the proportion of NPC patients in whom less than two second locus antigens were detectable. The second confirmatory study also demonstrated the same phenomenon at a high level of statistical significance, and furthermore showed a significant elevation among the NPC patients of the frequency of HL-A2. Both the elevation of the HL-A2 frequency and the deficit of detectable second locus antigens remained significant after application of the most conservative correction factor for the number of antigens investigated. Various sources of bias have been considered and appear not to have appreciably influenced the results. The results are discussed in terms of the postulated genetic basis of the elevated risk for NPC among the Chinese. Aspects Immunogenetiques de L'Epithelioma du Rhino-Pharynx. I. Diffeerences du Profill des Antigenes HL-A Chez les Malades et Dans les Groupes Temoins Le present article rapporte les resultats de deux etudes visant a comparer le profil des HL-A chez des malades (generalement des Chinois) atteints d'epithelioma du rhino-pharynx (ERP) et chez des temoins convenablement selectionnes. La premiere etude a mis en evidence une augmentation sensible de la proportion de cas d'ERP ou l'on decelait moins de deux antigenes du second locus. L'etude confirmative a egalement mis en evidence le meme phenomene et montre que sa signification statistique est importante; en outre, elle a permis de constater que la frequence des HL-A2 et la rarete des antigenes du second locus sont restees significatives me mlorsque l'on a applique le facteur de correction le plus raisonnable au nombre d'antigenes observe. Diverses sources de distrosion ont ete envisagees qui semblent ne pas avoir beaucoup influence les resultats. Les auteurs analysent ces resultats sous l'angle de la base genetique postulee du risque eleve d'ERP chez les Chinois.

Journal ArticleDOI
TL;DR: Human lymphocytes tested for cytotoxicity against T24 cells derived from a carcinoma of the bladder and against cell cultures derived from other tissues showed results in agreement with those obtained by others who used the standard MCT that measures target‐cell destruction and influences on target‐ cell proliferation.
Abstract: Human lymphocytes (purified from defibrinated venous blood using gelatin sedimentation, nylon column incubation, and Tris NH4Cl lysis of contaminating erythrocytes) were tested for cytotoxicity (CTX) against T24 cells derived from a carcinoma of the bladder and against cell cultures derived from other tissues. The CTX was assessed in a modified microcytotoxicity test (MCT) where loss of 3H-proline prelabelled monolayer target cells from the surface of micro-wells indicates destruction of these cells. The number of target cells that remained attached after incubation with lymphocytes (measured as residual 3H-counts) was compared to the number that remained attached after incubation with control lymphocytes. The results were classified into three categories: (1) specific CTX (destruction only of T24 cells); (2) non-specific CTX (destruction ofT24 cells as well as other target cells); and (3) negative (no destruction of any type of target cell). Specific CTX for T24 cells was seen more often with lymphocytes from bladder cancer patients (10/27) than from other patients and normal individuals (2/49) (p <0.001) which suggests that this is a disease-related phenomenon. By contrast, non-specific CTX occurred with equal frequency amopg bladder patients (6/27) and other patients (9/36), although less frequently among normal individuals (0/13). In addition, lymphocytes that showed specific CTX for T24 cells were found more often in patients with early or superficial bladder cancer (8/15) and less often in patients with advanced bladder cancer (2/12). These results are in agreement with those obtained by others who used the standard MCT that measures target-cell destruction and influences on target-cell proliferation.

Journal ArticleDOI
TL;DR: The data support the idea that the œstriol proportion, especially among young women, is a correlate of subsequent breast cancer risk.
Abstract: Œstrone (El), œstradiol (E2) and œstriol (E3) were measured in the urine of Asian and North American women aged 15-19, 20-24 and 30-39 years, during the follicular and luteal phases of the menstrual cycle. Each urine specimen was characterized by its œstriol proportion, E3/(E1+E2+E3). In each age group and cycle phase Asians had lower concentrations of œstrone and œstradiol and a higher oestriol proportion than North Americans. The differences were greatest in the youngest age group. Differences between the women from two North American cities or between women from three Asian areas were small. The data support the idea that the œstriol proportion, especially among young women, is a correlate of subsequent breast cancer risk.

Journal ArticleDOI
TL;DR: It is suggested that oesophageal cancer is more likely to occur among “traditional” Chinese who maintain dietary patterns which include Samsu and the drinking of beverages at hot temperatures, but avoid the bland foodstuffs not native to their culture.
Abstract: Analysis of a hospital-based case-control study of esophageal cancer among Singapore Chinese (composed of Cantonese Hokkien Teochew and other dialect groups) revealed the following statistically significant risk factors for both sexes: 1) belonging to either Hokkien or Teochew dialect group; 2) consuming beverages at temperatures stated subjectively to be burning hot before illness; and 3) smoking Chinese cigarettes. Additional risk factors for males were birth in China and consumption of Samsu (Chinese wine). Bread potato and banana consumption was reported at significantly lower levels in male esophagus cancer patients than controls. Esophageal cancer was less common in males who attended school for more than 8 years. Multivariate analysis (joint influence of selected variables) confirmed the strong effects of dialect group and beverage temperature for both sexes. For females Chinese cigarette smoking remained a risk factor; for males Samsu consumption. Smoking western cigarettes and drinking strong liquors were not significantly related for either sex. These findings suggest that esophageal cancer is more likely to occur among traditional Chinese who maintain dietary patterns which include Samsu and scalding beverages but avoid bland foodstuffs not native to the culture. The greater risk in Teochew and Hokkien may be due in part to beverage temperature since "burning hot" was cited more frequently in these dialect groups. However these differences are based on subjective impressions and require further verification.

Journal ArticleDOI
TL;DR: TPA induced striking morphological changes including a decrease in cell size, suggesting that it may enhance cell division by increasing the number of cells per unit area required for cell‐to‐cell contact and confluence to be attained.
Abstract: When the tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), was added to freshly seeded cultures of human diploid fibroblasts, cell growth was inhibited for 24–48 h and then proceeded at the same rate as in controls. After the control cultures had become confluent, cell division and the incorporation of tritiated thymidine continued in treated cultures, and the cell yield after 9–11 days was increased by as much as 50% compared to untreated cultures. TPA induced striking morphological changes including a decrease in cell size, suggesting that it may enhance cell division by increasing the number of cells per unit area required for cell-to-cell contact and confluence to be attained. TPA produced similar effects when added to growing cultures of NIH Swiss 3T3 mouse embryo and chick embryo fibroblasts. Continuous cultivation of human fibroblasts in the presence of TPA increased the cell yield for approximately five successive passages but did not increase the total number of population doublings over the entire life-span of the cultures.

Journal ArticleDOI
TL;DR: It is concluded that cells of BL biopsies may contain EBNA in addition to the EBV‐related membrane antigen previously described, providing further evidence that BL cells from African patients resemble non‐producer lymphoblastoid cell lines in containing EBNA and therefore appear to be transformed by EBV.
Abstract: Cells from Burkitt lymphoma (BL) biopsies were examined for Epstein-Barr virus (EBV)-associated antigens by complement fixation (CF) tests and by the anti-complement immunofluorescence (ACIF) test. In CF tests, anticomplementary factors made it difficult to test all the biopsies available. However, biopsies from 19 patients were effectively tested and 12 of these (including two from one patient) contained antigen reacting with a battery of human sera with antibody to EBV but not with sera lacking such antibody. Technical difficulties prevented further characterization of the EBV-related antigens in the biopsies. Application of the ACIF test to BL revealed the presence of EBV-related nuclear antigen in biopsies from 11 of 13 patients. Absorption studies indicated that the nuclear antigens of the biopsies were closely related antigenically to the EBV-determined nuclear antigen (EBNA) previously described in lymphoblastoid cell lines. It is concluded that cells of BL biopsies may contain EBNA in addition to the EBV-related membrane antigen previously described. The results provide further evidence that BL cells from African patients resemble non-producer lymphoblastoid cell lines in containing EBNA and therefore appear to be transformed by EBV.

Journal ArticleDOI
TL;DR: The findings suggest that EB virus is harboured in peripheral lymphocytes of IM patients as a non‐productive unexpressed infection which is activated to produce virus in vitro, the particles released then infecting neighbouring cells to give transformed lines.
Abstract: Transformation to continuous cell lines has been studied in cultures of peripheral leukocytes from infectious mononucleosis (IM) patients and in co-cultures of IM leukocytes and foetal cord blood leukocytes of opposite sex. The transformed cells in the co-cultures were of mixed origin with foetal cells usually predominating. Neutralizing antisera to EB virus markedly reduced or abolished the incidence of transformation in IM leukocyte cultures. This effect was not due to cytotoxicity and followed the pattern seen with cultures where transformation was known to depend on the intercellular transfer of infectious EB virus. The findings suggest that EB virus is harboured in peripheral lymphocytes of IM patients as a non-productive unexpressed infection which is activated to produce virus in vitro, the particles released then infecting neighbouring cells to give transformed lines. The differences between this mechanism and the one whereby lines arise in culture from the malignant cells of Burkitt's lymphoma are considered, and their significance is discussed.

Journal ArticleDOI
Takeo Kakunaga1
TL;DR: A31‐714 cells, a subclone derived from BALB/3T3, did not produce transformed foci when kept under culture conditions of density‐dependent inhibition after treatment with 4NQO in either the growing or the non‐growing state, and one cell generation is required for the fixation of transformation.
Abstract: A31-714 cells, a subclone derived from BALB/3T3, did not produce transformed foci when kept under culture conditions of density-dependent inhibition after treatment with 4NQO in either the growing or the non-growing state. The transformation frequency increased to nearly maximum level only when the cells had undergone more than four cell generations after 4NQO-treatment. Cells which were first kept in a non-growing state after 4NQO-treatment, rapidly lost the ability to exhibit transformation even when they were subsequently returned to a growing state. On the other hand, the cells which were allowed one cell replication soon after 4NQO-treatment retained their ability to produce transformed foci even after being kept in the non-growing state for as long as 6 days thereafter. These results suggest that one cell generation is required for the fixation of transformation, and more than four cell generations are required for the expression of the transformed state.

Journal ArticleDOI
TL;DR: The results suggest that antigens detected on these tumours were embryonic components which were immunogenic in the tumor‐bearing host, although they were not capable of inducing tumour‐rejection reactions in immunized rats.
Abstract: Lymph-node cells from rats bearing tumours apparently lacking in tumour rejection antigens were cytotoxic in vitro for cultured tumour cells. The specificities of these reactions differed, however, from those demonstrated with immunogenic chemically-induced rat tumours since cross-reactivity was observed, especially between tumours of the same histological type. This was most clearly demonstrated in tests with rat mammary carcinomas where tumour-bearer lymph-node cells were cytotoxic for a range of mammary carcinomas including spontaneously arising and chemically-induced tumours. The reactivities of tumour-bearer lymph-node cells could be blocked by pre-treating target cells with serum of tumour-bearing rats and also by sera of multiparous rats. Conversely, tumour-bearer sera were highly effective in blocking embryo cells from attack by sensitized LNC from multiparous rats. The results suggest that antigens detected on these tumours by the in vitro assay were embryonic components which were immunogenic in the tumor-bearing host, although they were not capable of inducing tumour-rejection reactions in immunized rats.

Journal ArticleDOI
TL;DR: Interferon treatment of murine C‐type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation but cell‐associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited.
Abstract: Interferon treatment of murine C-type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation. When such cells are subcultured in the presence of interferon, synthesis of extracellular C-type virus remains depressed until the interferon treatement is discontinued. Cell-associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited. Several possibilities to explain this discrepancy are tested. The most likely hypothesis is that interferon treatment primarily inhibits virus release.

Journal ArticleDOI
TL;DR: Data from Iceland show that breast cancer has increased very markedly in Iceland during this period, and that as the overall incidence has risen, so the age‐incidence curve has changed in shape, the relation between the shape and theOverall incidence being the same as that now observed in other countries.
Abstract: Among different populations, the shape of the age-incidence curve for breast cancer is strongly related to the overall incidence of breast cancer in the respective population. Data are available from Iceland for the period 1911–1972. These data show that breast cancer has increased very markedly in Iceland during this period, and that as the overall incidence has risen, so the age-incidence curve has changed in shape, the relation between the shape and the overall incidence being the same as that now observed in other countries. The change in shape is shown to be explicable entirely as a cohort phenomenon, each decade of birth cohort having an age-incidence curve of similar shape, but with different overall incidence. Data from some other regions of the world indicate that many of the present differences in the shape of the age-incidence curve may be the reflection of cohort phenomena.

Journal ArticleDOI
TL;DR: The two specimens revealed a close similarity also in some other physicochemical, chemical and immunological properties.
Abstract: Alpha-fetoprotein of the rat was immunochemically purified and characterized. Mouse α-fetoprotein, which cross-reacts with antibodies to rat α-fetoprotein, was also purified. Rat α-fetoprotein was heterogeneous in disc electrophoresis and isoelectric focusing and had two different isoelectric points at pH 4.76 and 5.05. Mouse α-fetoprotein was homogeneous when analyzed similarly. The molecular weight of both rat and mouse α-fetoprotein was 70,000 as determined by gel electrophoresis in the presence of sodium dodecyl sulfate. The two specimens revealed a close similarity also in some other physicochemical, chemical and immunological properties. Purification et Caracterisation Chimique de L'α-Fœtoproteine de Rat et de Souris L'α-fœtoproteine de rat a ete immunochimiquement purifiee et caracterisee. L'α-fœtoproteine de souris, qui a des rections croisees avec les anticorps contre l'α-fœtoproteine de rat, a egalement ete purifiee. L'α-fœtoproteine de rat est heterogene, comme l'indiquent l'electrophorese en gel d'acrylamide et le reperage du point isoelectrique, et elle a deux points isoelectriques differents a pH 4.76 et 5.05. Les měmes analyses ont montre que l'α-fœtoproteine de souris est homogene. Le poids moleculaire des α-fœtoproteines de rat et de souris est de 70 000, comme on l'a determine par electrophorese en gel en presence de dodecyle sulfate de sodium. On a egalement constate chez les deux specimens une etroite ressemblance du point de vue de quelques autres proprietes physicochimiques. chimiques et immunologiques.

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TL;DR: The failure to find S‐tropic viruses in known preparations of leukemogenic murine type‐C viruses and their presence in tissues from normal animals suggest that S‐ Tropic viruses may play a normal physiologic role in mice.
Abstract: A survey was undertaken to determine the prevalence of S‐tropic (xenotropic) murine type‐C viruses in continuous cell lines, leukemia virus preparations, and spleens of normal mice from various commonly used strains. Fifteen of 18 cell lines established from normal cells and transplantable tumors produced infectious type‐C viruses. For all cell lines examined, the viral isolates were either N‐, B‐, or NB‐tropic, while S‐tropic viruses were not detected. Two cell lines derived from normal tissues, however, had S‐tropic viruses which could be induced by treatment with 5‐bromodeoxyurdine, whereas cell lines derived from transplantable tumors were non‐inducible. Nine standard leukemia virus preparations likewise do not contain S‐tropic viruses. In contrast, S‐tropic viruses were recovered from spleens of normal weanling mice from six of 13 strains, indicating that the expression of S‐tropic virus is relatively common in disease‐free animals. The failure to find S‐tropic viruses in known preparations of leukemogenic murine type‐C viruses and their presence in tissues from normal animals suggest that S‐tropic viruses may play a normal physiologic role in mice.

Journal ArticleDOI
TL;DR: Findings support the view thatymphoblast transformation and EA induction and inhibition of lymphoblast colony formation are induced by the same type of viral particle.
Abstract: Epstein-Barr virus (EBV)-neutralizing (N) antibodies were determined in human sera by three techniques based on (1) early antigen (EA) synthesis in lymphoblasts (NEA); (2) inhibition of colony formation by lymphoblasts (NICF); and (3) cordblood lymphocyte transformation (NLT). A good correlation was noted between the NEA and NICF titres of 41 sera so tested (r = 0.73). The correlation between NEA or NICF and NLT titres was less pronounced (r = 0.54 and 0.56), possibly because only 22 sera were tested by the last method. Limited to concordant sera, i.e. sera with either both high or both low titres of antibodies to EB viral capsid antigens (VCA) and to EBV-determined cell membrane antigens (MA), the N titres determined by the three methods showed a good correlation with anti-MA titres (r = 0.83, 0.80 and 0.68, respectively) as did the few discordant sera with high anti-MA but low anti-VCA titres. However, some discordant sera with low anti-MA and high anti-VCA titres also showed substantial N titres. The mean anti-VCA titres were equal in the concordant and discordant groups (553), the anti-MA (BT) titres were 25 and ⩽ 1.4, respectively, whereas the neutralization titres were 209 (NEA), 204 (NICF) and 523 (NLT) in the concordant, as compared to 128, 74 and 99 in the discordant group. These findings support the view that lymphoblast transformation and EA induction and inhibition of lymphoblast colony formation are induced by the same type of viral particle. Comparaison des Tests de Neutralisation de L'Ebv Bases sur L'Infection Abortive ou la Transformation de Cellules Lymphoides et de Leur Relation Avec les Anticorps Reactifs de La Membrane (Anti-MA) Les anticorps neutralisant (N) le virus d'Epstein-Barr (EBV) ont ete recherches dans des serums humains par trois techniques basees sur 1) la synthese de l'antigene precoce (EA) dans les lymphoblastes (NEA), 2) l'inhibition de la formation de colonies par les lymphoblastes (NICF) et 3) la transformation des lymphocytes (NLT). On a observe une bonne correlation entre les titres de NEA et de NICF de 41 serums ainsi testes (r = 0.73). La correlation entre les titres de NEA ou de NICF et les titres de NLT etait moins prononcee (r = 0.54 et 0.56), peut-etre parce que 22 serums seulement avaient ete testes par la derniere methode. Si l'on se limitait aux serums concordants, c'est-a-dire les serums ayant tous des titres eleves ou faibles d'anticorps contre les antigenes des capsides virales EB (VCA) et les antigenes de la membrane (MA) determines par l'EBV, on notait une bonne correlation entre les titres de N obtenus avec les trois methodes et les titres d'anti-MA (r = 0.83, 0.80 et 0.68 respectivement), comme pour les quelques serums discordants ayant des titres eleves d'anti-MA mais de faibles titres d'anti-VCA. Toutefois, les titres de N etaient egalement considerables dans quelques serums discordants a faible titre d'anti-MA et a titre eleve d'anti-VCA. Les titres moyens d'anti-VCA etaient equivalents dans les serums concordants et discordants (533), les titres d'anti-MA (BT) etaient respectivement de 25 et < 1.4, alors que les titres de neutralisation atteignaient 209 (NEA), 204 (NICF) et 523 (NLT) dans les serums concordants, contre 128, 74 et 99 dans le groupe discordant. Ces resultats confirment l'hypothese selon laquelle la transformation des lymphoblastes, l'induction d'EA et l'inhibition de la formation de colonies de lymphoblastes sont provoquees par le měme type de particule virale.

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TL;DR: It was observed that inducible mice are approximately 12 times more sensitive to 3‐methylcholanthrene‐induced tumorigenesis than their non‐inducible littermates.
Abstract: Using a genetic system in which aryl hydrocarbon hydroxylase (AHH) inducibility segregates, it was observed that inducible mice are approximately 12 times more sensitive to 3-methylcholanthrene-induced tumorigenesis than their non-inducible littermates. The type of parental cross (maternal influence) plays no role in this sensitivity. Hostregulated expression of the group-specific (gs) antigen of type-C RNA viruses, although also segregating in this genetic system, does not seem to play a major role in this enhanced susceptibility to 3-methylcholanthrene carcinogenesis. Results are discussed with the view that the enhanced sensitivity of the AHH-inducible animals probably results from rapid and efficient metabolism of the chemical to its ultimate carcinogenic form.

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TL;DR: The results strengthen the validity of the lymphocyte stimulation test as an assay for tumor‐specific reaction and correlated well with the in vivo immune reactivity indicated by skin tests.
Abstract: 3 M KCl-extracts prepared from human tumors (14 sarcoma, 2 astrocytoma, 3 Wilm's nephroblastoma and 1 melanoma) and from non-malignant tissues (8 muscle, 4 skin, 2 cartilage, 1 kidney, 2 brain and 1 bone marrow) have been used to stimulate autohgous and allogeneic lymphocytes and as antigen in autologous skin tests. The results of the lymphocyte stimulation by autologous tumor-biopsy cells and their KCl-extracts were concordant. Moreover, these in vitro results correlated well with the in vivo immune reactivity indicated by skin tests. Tumor-cell suspensions were weak allogeneic stimulators, and KCl-extracts were stimulatory only after presensitization. When a tumor-cell sample and its KCl-preparation were used in autologous and 11 allogeneic tests the degree of autologous stimulation with tumor cells was as high as the highest allogeneic one and the KCl-extract stimulated the autologous lymphocytes to the same degree. The results strengthen the validity of the lymphocyte stimulation test as an assay for tumor-specific reaction.

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TL;DR: The two‐ and three‐stage ACIF procedures yield comparable anti‐EBNA titers with non‐anti‐complementary sera.
Abstract: Titration of anti-complementary human sera may yield false negative or prozone reactions in anti-complement immunofluorescence (ACIF) tests for antibodies to Epstein-Barr virus-associated nuclear antigen (EBNA) when the human complement (C') is added to the serum dilutions prior to charging of the target cell smears (two-stage ACIF test). This effect of anti-complementary sera and with it a source of error is avoided by using a three-stage ACIF technique; that is, when the target cell smears are successively overlayed with serum dilutions, C' and fluorescein isothiocyanate-conjugated antibodies to human βC/βA globulins. The two- and three-stage ACIF procedures yield comparable anti-EBNA titers with non-anti-complementary sera.