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Showing papers in "Journal of the National Cancer Institute in 1983"


Journal ArticleDOI
TL;DR: Results show that BHA is carcinogenic in the forestomach of F344 rats, considered to be associated with neoplasias.
Abstract: Butylated hydroxyanisole (BHA) was added at levels of 0.5 and 2.0% to the diet of inbred F344 rats for 2 years. The higher dose of BHA induced a significant increase in the incidence of papilloma and squamous cell carcinoma in both sexes. Both the higher and lower doses increased the incidences of hyperplasia of the forestomach, considered to be associated with neoplasias. The incidences of these neoplastic changes were dose-dependent. Neoplastic changes in other organs were not increased significantly by BHA. These results show that BHA is carcinogenic in the forestomach of F344 rats.

633 citations


Journal ArticleDOI
TL;DR: Cette revue met l'accent sur quelques sujets d'evolution recente: chimie des marqueurs glycolipidiques associes aux tumeurs and regis par le developpement, facteurs affectant l'expression des Glycolipides a la surface des cellules, and application possible des marquettes au traitement and au diagnostic du cancer humain.
Abstract: Cette revue met l'accent sur quelques sujets d'evolution recente: 1) chimie des marqueurs glycolipidiques associes aux tumeurs et regis par le developpement; 2) facteurs affectant l'expression des glycolipides a la surface des cellules, et 3) application possible des marqueurs glycolipidiques au traitement et au diagnostic du cancer humain

616 citations


Journal ArticleDOI
TL;DR: Entrapment of surface epithelium within the ovarian stroma was proposed as an initial event in the pathogenesis of cystadenocarcinoma of the ovary and animal experiments suggested that gonadotropin excess and stromal stimulation may result by disturbing normal feedback inhibition between ovarian and pituitary or by destroying ovarian follicles.
Abstract: Entrapment of surface epithelium within the ovarian stroma was proposed as an initial event in the pathogenesis of cystadenocarcinoma of the ovary. Subsequent events, including differentiation, proliferation, and eventual malignant transformation of the entrapped epithelium, may occur as a consequence of stimulation by estrogen or estrogen precursors. These events were more likely when the steroid producing stroma itself had been stimulated by high gonadotropins. Animal experiments suggested that gonadotropin excess and stromal stimulation may result by disturbing normal feedback inhibition between ovary and pituitary or by destroying ovarian follicles. By analogy, in humans, a number of common chemicals and drugs may increase gonadotropins by enhancing estrogen degradation in the liver or by directly stimulating production by the pituitary. Elevated gonadotropins may also result via mechanisms that cause primary ovarian failure including pelvic irradiation, exposure to chemicals or metabolites toxic to follicles, or ovarian infections such as mumps.

606 citations


Journal ArticleDOI
TL;DR: Findings indicate a coordinate morphological and biochemical interconversion of neuroblastoma SK-N-SH cells and reveal a plasticity in phenotypic expression in malignant neuronal cells.
Abstract: This study was undertaken to determine whether the two type of cells (one neuroblast-like and the other epithelial in appearance) of the human neuroblastoma line SK-N-SH in culture undergo morphological interconversion, whether conversion is bidirectional, and whether there are coordinate neurochemical changes. Phenotypic analysis of serially isolated neuroblast clones (SH-SY, SH-SY5, SH-SY5Y) revealed conversion to epithelial-like cells. Conversely, conversion also was promoted from an epithelial-like clone (SH-EP) to neuroblastic subclones. Cell origin could be verified because of a marker chromosome specific to SH-EP. Only neuroblastic subclones of SH-EP contained activities for tyrosine hydroxylase and dopamine-beta-hydroxylase, enzymes unique to catecholamine neurons; epithelial-like cells lacked activities for these enzymes. These findings indicate a coordinate morphological and biochemical interconversion of neuroblastoma SK-N-SH cells and reveal a plasticity in phenotypic expression in malignant neuronal cells.

586 citations



Journal ArticleDOI
TL;DR: Pregnancy exerted a strong protective effect against ovarian cancer, which increased with the number of live-born children, and women with ovarian cancer had more frequently used menopausal hormones in cyclic fashion compared to controls.
Abstract: Reproductive experiences and family history were assessed in 215 white females with epithelial ovarian cancer and in 215 control women matched by age, race, and residence. Pregnancy exerted a strong protective effect against ovarian cancer, which increased with the number of live-born children. After adjustment for parity, an effect of age at first live birth and breast-feeding was not apparent. Menstrual events did not differ significantly between cases and controls, although cases were more likely to have had an earlier menopause and less likely to have had a surgical menopause. Women with ovarian cancer had more frequently used menopausal hormones in cyclic fashion compared to controls. Regarding family history, women with ovarian cancer more frequently reported consanguinity in their ancestry and a highly frequency of primary relatives with cancer of the colon, lung, ovary, and prostate gland.

286 citations


Journal ArticleDOI
TL;DR: A modified hormonal milieu in the mother appears to be important in the later development of testicular cancer in her sons, and exposure of the mother to exogenous estrogen during pregnancy created a significant risk in the son.
Abstract: In this case--control study of 108 cases of testicular cancer in men under 30 years of age, cryptorchidism was a major risk factor [relative risk (RR) = 9.0]. Low birth weight was also associated with increased risk (RR = 3.2). Having severe acne at puberty was protective (RR = 0.37). Interviews with mothers of cases revealed that exposure of the mother to exogenous estrogen during pregnancy created a significant risk in the son (RR = 8.0). In first pregnancies, excessive nausea indicated an increased risk of testicular cancer (RR = 4.2). Increased body weight in the mother also increased the risk. The relation between these factors and testicular hypoplasia is discussed. Severe perimenopausal menorrhagia was a factor in the mother associated with reduced risk of testicular cancer in the son (RR = 0.10). A modified hormonal milieu in the mother appears to be important in the later development of testicular cancer in her sons.

282 citations


Journal ArticleDOI
TL;DR: In this paper, a comparison of 260 patients from Buffalo with cancer of the prostate gland was made with two different control series of similar size and age distribution, regardless of the control group, risk of prostate cancer gained with increases in ingestion of retinoids, animal fats, and vitamin C.
Abstract: In vivo, in vitro, prospective, and retrospective epidemiologic inquiries have suggested that retinoids inhibit cancer, and fats have been hypothesized to enhance and ascorbic acid to reduce cancer risk. Comparison of 260 patients from Buffalo with cancer of the prostate gland was made with two different control series of similar size and age distribution. Regardless of the control group, risk of prostate cancer gained with increases in ingestion of retinoids, animal fats, and vitamin C. These anomalous findings may be due to peculiarities in methodology. From the possible specificity of effect of the nutrients studied, as shown in experimental animals and in vitro, a hypothesis could be made that a substance like vitamin A or C, which may inhibit certain cancers, also may enhance risk of other cancer types or have neither effect.

263 citations


Journal ArticleDOI
TL;DR: Lung cancers were induced in inbred W rats by cadmium chloride aerosols by inducing a dose-dependent incidence of primary lung carcinomas of the following types: adenocarcinomas, epidermoid (squamous cell) carcinomas, combined epidersmoid carcinomas and adenOCarcinoma, and mucoepidermoids carcinomas.
Abstract: Lung cancers were induced in inbred W rats by cadmium chloride aerosols. For 18 months, 120 male W rats were continuously exposed to cadmium chloride aerosols with cadmium (Cd) concentrations of 12.5, 25, and 50 micrograms/m3, respectively. For the same period of time, 41 rats were kept in filtered air; these rats served as the control group. The survivors were killed 13 months after the end of the inhalation experiments. Histopathologic examination revealed a dose-dependent incidence of primary lung carcinomas of the following types: adenocarcinomas, epidermoid (squamous cell) carcinomas, combined epidermoid carcinomas and adenocarcinomas, and mucoepidermoid carcinomas. The incidence of lung carcinomas was 71.4% in the group exposed to 50 micrograms Cd/m3, 52.6% in the group exposed to 25 micrograms Cd/m3, and 15.4% in the group exposed to 12.5 micrograms Cd/m3. None of the controls developed lung carcinomas. At the end of the experiment, the remaining Cd concentrations in the lungs were relatively high, almost at the same level as those in the livers.

206 citations


Journal ArticleDOI
TL;DR: For each cohort, recent smoking cessation rates for men have exceeded those for women, and maximum exposure to cigarette smoking probably occurred among men who are now in their seventh and eighth decades, by contrast, peak exposure to smokingProbably occurred among women who is now only in their fifth and sixth decades.
Abstract: Trends in cigarette smoking among successive cohorts of men and women were reconstructed from smoking histories of respondents to the 1978-80 Health Interview Surveys. Estimated smoking rates among the older cohorts were then adjusted for the differential mortality of cigarette smokers and nonsmokers. By 1920, over half of the young male population smoked cigarettes. Not until 1950 did more than a third of the young female population smoke cigarettes. The proportion of men who ever smoked cigarettes progressively declined with each successive cohort born after 1920. By contrast, the proportion of women who ever smoked declined only among cohorts born after 1940. Cessation of cigarette smoking from age 30 years onward was observed for all cohorts of men. Cessation rates accelerated for men who reached age 30 after 1960. By contrast, smoking cessation from age 30 was observed only for women who reached age 30 after 1950. Cessation rates accelerated only for women who reached age 30 after 1970. For each cohort, recent smoking cessation rates for men have exceeded those for women. Maximum exposure to cigarette smoking probably occurred among men who are now in their seventh and eighth decades. By contrast, peak exposure to smoking probably occurred among women who are now only in their fifth and sixth decades.

195 citations


Journal ArticleDOI
TL;DR: Parity appeared to exert its predominant effect on risk of cancer of the right colon in Australia and showed a dose-response effect in multiple logistic analysis.
Abstract: A community-based case control study of the effect of reproductive factors on risk of large bowel cancer in Australia is described. The study involved 155 cases (99 colon cancer 56 rectal cancer) and 311 controls who were interviewed with regard to pregnancies and their outcomes lactation menstrual history and oral contraceptive (OC) use. Increasing parity was associated with a decreasing risk of colon cancer: para 0 relative risk (RR)=1; para 1-2 RR=0.9 95% confidence interval (CI)=0.4-1.8; para >or= 3 RR=0.4 95% CI=0.2-0.8; later age at 1st live birth (AFLB) was associated with increasing risk (AFLB or= 26 years RR=2.7 95% CI=1.2-6.2). These effects were independent of each other. Parity appeared to exert its predominant effect on risk of cancer of the right colon. OC use was more common among controls than cases (RR=0.5; 95% CI=0.3-1.2 for ever vs never users) and showed a dose-response effect in multiple logistic analysis. The pattern of point estimate RR for rectal cancer was largely congruent with those for colon cancer but was not significantly different from 1.0. (authors)

Journal ArticleDOI
TL;DR: It is demonstrated that the apparent protective effect of vitamin A in the 30- to 49-year age group (but not dietary fiber) was independent of the nondietary factors analyzed in this study (P less than .05).
Abstract: A case-control study is presented that estimates ovarian cancer risk for various factors, including diet. Data collected by interview between 1957 and 1965 for 274 white women aged 30-79 years with epithelial carcinoma of the ovary are compared to data similarly collected for 1,034 hospital controls. Relative risk estimates are presented for the total group as well as for premonopausal (ages 30-49) and postmenopausal (ages 50-79) are groups. In the total group, cancer risk increased with increasing age at first marriage (P less than .01) and previous history of benign breast disease (P less than 0.1), and risk decreased with increasing number of previous pregnancies (P less than .01). In the 50- to 79-year age group, a marginally significant trend for decreasing risk with increasing obesity was observed (P less than .10). There was no significant risk (i.e., P less than .10) associated with the consumption of alcohol, cigarettes, coffee, tea, total dietary protein, vitamin C, or fat at any age. In the 30- to 49-year age group only, increased risk (P less than .01) was seen in women reporting diets low in fiber and vitamin A from fruit and vegetable sources. Multiple regression analysis demonstrated that the apparent protective effect of vitamin A in the 30- to 49-year age group (but not dietary fiber) was independent of the nondietary factors analyzed in this study (P less than .05).

Journal ArticleDOI
TL;DR: It is demonstrated that stem cell renewal has a central role in determining the growth properties of tumors.
Abstract: A simple stem cell model of human tumor growth is presented. Three tumor cell populations are predicted: stem, transitional, and end cells. The properties of these cells are discussed in terms of their behavior in currently available technologies for investigation of cell kinetics and for their influence on clinical outcome. Stem cell renewal, transitional cell proliferation, and cell loss are analyzed mathematically to define their influence on the relative proportions of cell populations; it is demonstrated that stem cell renewal has a central role in determining the growth properties of tumors. The impact of a stem cell model on the use of tumor clonogenic assays as predictors of clinical outcome is discussed; opinions are expressed as to the definition of reasonable expectations for current experimental procedures.

Journal ArticleDOI
TL;DR: The results imply that hormonal factors in concentrations physiologically occurring in human serum may support the in vivo growth of ovarian tumors.
Abstract: Carcinoma cell lines established from 5 patients with advanced tumors of ovarian location were characterized by karyotypes and growth properties in serum-free medium. In early passages of the cultivation, the growth of cell lines derived from tumors of fairly differentiated histology was stimulated by human follicle-stimulating hormone or human chorionic gonadotropin-human luteinizing hormone. Cells obtained from poorly differentiated carcinomas were unresponsive to gonadotropins. The proliferation of cell lines derived from a malignant clear cell carcinoma and from the ovarian metastasis of an advanced mammary carcinoma was enhanced by cortisol. The results imply that hormonal factors in concentrations physiologically occurring in human serum may support the in vivo growth of ovarian tumors.

Journal Article
TL;DR: A new cell line (BV173) derived from a patient with Philadelphia chromosome (Ph1)-positive acute leukemia was compared with the Ph1-positive K562 and NALM-1 lines, which display the phenotypic characteristics of erythroid and pre-B cells, respectively.
Abstract: A new cell line (BV173) derived from a patient with Philadelphia chromosome (Ph1)-positive acute leukemia was compared with the Ph1-positive K562 and NALM-1 lines, which display the phenotypic characteristics of erythroid and pre-B cells, respectively. BV173 cells retained the Ph1 chromosome and had the morphologic and cytochemical features of undifferentiated blast cells. They lacked the membrane characteristics of mature B- or T-lymphocytes and did not react with monoclonal antibodies to the myelomonocytic cell lineage. Although they reacted with anti-glycophorin A antiserum, they failed to produce hemoglobin after butyric acid treatment. This line was similar to NALM-1 in that it bore common acute lymphoblastic leukemia antigen and la-like antigen, reacted with monoclonal antibodies directed against early stages of hematopoietic cell differentiation, and presented the nuclear enzyme terminal deoxynucleotidyl transferase. However, it differed from NALM-1 because it did not express cytoplasmic IgM, a marker of pre-B-cells. The new line can be considered a clonal expansion of leukemia cells blocked at an earlier differentiation stage than that for the other Ph1-positive cell lines.

Journal ArticleDOI
TL;DR: The histologic and mathematical evaluations indicated that the investigated compounds had distinct carcinogenic potencies and showed no tumor-producing effect in this system.
Abstract: The biologic activity of eight highly purified polycyclic aromatic hydrocarbons (PAH) widely distributed in the human environment was tested in the respiratory tracts of rats. These studies were performed for the examination of carcinogenic activity of the compounds and determination of a dose-response relationship. The lung implantation method was used in 3-month-old female OM rats. A dose-response relationship was obtained for benzo[a]pyrene (BaP), anthanthrene (ANT), benzo[b]fluoranthene (BbF), indeno[1,2,3-cd]pyrene (IND), benzo[j]fluoranthene (BjF), and benzo[k]fluoranthene (BkF). Benzo[e]pyrene and benzo[ghi]perylene showed no tumor-producing effect in this system when given at doses of 5 mg. The histologic and mathematical evaluations indicated that the investigated compounds had distinct carcinogenic potencies. After probit analysis of the results, the carcinogenic potencies of PAH investigated in the lung implantation model rank as follows: BaP, 1.00; ANT, 0.19; BbF, 0.11; IND, 0.08; BkF, 0.03; and BjF, 0.03.

Journal ArticleDOI
TL;DR: Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used in the evaluation of cancer patient survival experience for almost 10% of the U.S. population, suggesting increasing rates for cancers of the colon, lung, and prostate gland, whereas there were no definite increases for cancer of the female breast and corpus uteri.
Abstract: Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used in the evaluation of cancer patient survival experience for almost 10% of the U.S. population. This first report contains actuarial (life table) survival analysis on 368,263 patients with first primary cancer diagnosed in 1973-79 from nine SEER areas: the entire States of Connecticut, Iowa, New Mexico, Utah, and Hawaii and the metropolitan areas of Atlanta, Detroit, San Francisco, and Seattle. Both observed and relative survival rates were shown for whites and blacks, sex, age, primary site, and time period (each yr, 1973-78). The largest racial difference in survival was for cancer of the corpus uteri: 87% 5-year relative survival rate for white females versus only 54% for black females. Survival rates varied considerably by primary site. For most sites, as age increased the relative and observed survival rates decreased. Analysis of relative survival rates by ech year of diagnosis, 1973-78, and for each year following diagnosis suggested increasing rates for cancers of the colon, lung, and prostate gland, whereas there were no definite increases for cancers of the female breast and corpus uteri. A dramatic increase in survival from acute lymphocytic leukemia was found for children under 15 years of age, with the 4-year relative survival rate increasing from 51% among those diagnosed in 1973-75 to 65% for those diagnosed in 1976-78.


Journal ArticleDOI
TL;DR: Examination of lung cancer mortality among a cohort of white underground uranium miners in the Colorado plateau finds that differences between miners' and nonminers' mortality rates are substantially higher for smokers than for nonsmokers.
Abstract: This report examines lung cancer mortality among a cohort of white underground uranium miners in the Colorado plateau and is based on mortality follow-up through December 31, 1977. The analytic methods represent a miner's annual age-specific lung cancer mortality rate as the (unspecified) rate among nonsmoking men born at the same time and with no mining history, multiplied by the relative risk factor R. This factor depends on the miner's total exposures to radon daughters [in working level months (WLM) and to cigarettes (in packs), accumulated from start of exposure until 10 years before his current age. Among those examined, the relative risk function giving the highest likelihood of the data was R = (1 + 0.31 X 10(-2) WLM)(1 + 0.51 X 10(-3) packs). This multiplicative function specifies that ratios of mortality rates for miners versus nonminers with similar age and smoking characteristics do not depend on smoking status. By contrast, differences between miners' and nonminers' mortality rates are substantially higher for smokers than for nonsmokers. The data rejected (P = .01) several additive functions for R that specify relative risk as a sum of components due to radiation and to cigarette smoking. Cumulative exposures to both radiation and cigarettes gave better fits to the data than did average annual exposure rates. Age at start of underground mining had no effect on risk, after controlling for age at lung cancer death, year of birth, and cumulative radiation and smoking exposures.

Book ChapterDOI
TL;DR: The rapidly advancing technologies of computers, cell fusion, and genetic engineering are all interrelated through the underpinnings of molecular biology to offer us unparalleled opportunities in biological research, which should translate into more effective treatments for cancer in this decade.
Abstract: Biotherapy represents a new modality of cancer treatment. It utilizes biologicals and biological response modifiers. Many of these substances are of ‘natural’ origin eminating from mammalian cells as physiologic mediators of immune response and as substances active in the regulation of growth and maturation. With the advent of molecular biological techniques, hybridoma technology and computer applications, it is now possible to prepare these biological substances in highly purified form and in large quantities for use as medicinals. The expertise required to apply these biotherapeutic approaches to the treatment of cancer often involves the use of immunological and/or molecular biological capabilities. Because of the rather specialized expertise needed to understand and apply these substances as anticancer approaches, those individuals with expertise in the application of chemotherapy to patients with cancer are not necessarily well prepared for the translation of biotherapy to the clinic. Biotherapeutic approaches are broad and involve a whole range of physiological responses inherent in cancer biology. The approaches needed to bring these biotherapeutic capabilities to the clinic need to be considered carefully and the use of new techniques and new methods of application should be encouraged so as not to inhibit these potentially powerful anticancer approaches. As natural mediators, many biologicals have much less inherent toxicity than the drugs previously used in systemic cancer therapy. Therefore, the systems for translating these substances from the laboratory to the clinic should be restructured for the rapid translation of biotherapy to the patient.

Journal Article
TL;DR: It was concluded that the principal targets of the cytolytic JM-10 infection are B-cells, whereas the subsequent latent infection was found mostly in non-B-lymphocytes.
Abstract: Leukocyte suspensions derived from genetically Marek's disease (MD)-resistant N-line and MD-susceptible P-line chickens were fractionated at various times after exposure to the JM-10 clone of MD virus. At 3 and 5 days post exposure (DPE), during the productive-restrictive (cytolytic) phase, most infected spleen and thymus leukocytes were found to be low-density, nylon wool-adherent cells that possessed Fc receptors and surface Ia and IgM and were depleted by carbonyl iron treatment. This was true for leukocytes derived from N-line as well as those from P-line chickens. In contrast, most infected spleen cells derived from P-line chickens during the latent phase (i.e., after 7 DPE) were not found to have the above characteristics, with one exception: Ia antigen was demonstrated on the surface of latently infected cells. From these experiments it was concluded that the principal targets of the cytolytic JM-10 infection are B-cells, whereas the subsequent latent infection was found mostly in non-B-lymphocytes.

Journal ArticleDOI
TL;DR: Variations in incidence rates reveal population subgroups with particular tumor susceptibilities and may provide clues as to the relative influence of heredity and environment on patterns observed.
Abstract: Incidence rates of cancer among children aged 0-14 for the period 1970-79 have been generated with the use of data from the Greater Delaware Valley (GDV) Pediatric Tumor Registry. This population-based registry covers a 31-county area and has a pediatric base population of 2 million. During the period, approximately 2,300 cases of childhood cancer were diagnosed in the region. Incidence rates for all histologic types combined are similar to rates from other large surveys conducted in the United States and Western Europe. However, certain histology-specific rates in the GDV vary by race. In the GDV nonwhites relative to whites have higher rates of Wilms' tumor, soft tissue sarcomas other than rhabdomyosarcoma, and retinoblastoma. These contrasts are supported by surveys in African populations showing relatively higher rates of these tumors among African black children. GDV whites exceed nonwhites in incidence of acute leukemia, neuroblastoma, and Ewing's sarcoma. African black children also experience low rates of these tumors. The frequency of central nervous system tumors is similar for GDV whites and nonwhites, despite reports of a rarity of these neoplasms in African blacks. Variations in incidence rates reveal population subgroups with particular tumor susceptibilities and may provide clues as to the relative influence of heredity and environment on patterns observed.

Journal ArticleDOI
TL;DR: The data do not indicate an overall pattern of relative risks consistent with an effect on long-term second breast cancer risk of radiation exposure to the opposite breast incurred during adjunctive radiation therapy for a first breast cancer.
Abstract: Second breast cancer experience was examined for 27,175 primary breast cancer patients diagnosed in the State of Connecticut during 1935-75 with follow-up for second breast cancers through 1980. The overall ratio of observed to expected second breast cancers was 3.2. Relative risk was found to be inversely related to age at diagnosis and directly related to stage of the first breast cancer. The overall risk of second breast cancers was 711 per 100,000 person-years at risk. Risk of second breast cancers showed a similar relationship to age and stage as relative risk and was also directly related to calendar period of diagnosis of the first breast cancer. Some interactions were observed because patients less than 45 years old at diagnosis with positive nodes had elevated risks and relative risks in the early followup period, whereas less of an effect of stage on relative risk and risk was seen for older patients. The effect of the use of adjunctive radiation therapy on second breast cancer risk was also assessed by the ratio of the risk of second breast cancers for those patients who received both surgery and radiation to the risk of those patients who only received surgery being estimated for patients diagnosed during 1935-59 and for patients diagnosed during 1960-75. For both cohorts relative risks of 1.2-1.4 were found for the 5-year period immediately following diagnosis, likely resulting from the uncontrolled effect of stage in the analysis. Elevated long-term relative risks were not found for patients diagnosed during 1935-59. A long-term marginally statistically significant relative risk of 1.4 (greater than or equal to 10 yr after diagnosis) was found for patients diagnosed during 1960-75. The data do not indicate an overall pattern of relative risks consistent with an effect on long-term second breast cancer risk of radiation exposure to the opposite breast incurred during adjunctive radiation therapy for a first breast cancer.

Journal ArticleDOI
TL;DR: Fewer lung adenomas were induced by urethan in BALB/cBy mice than in the A/J or SWR/J mouse strains, suggesting that natural killer cells, deficient in bg/bg mice, played no major role in determining adenoma susceptibility in this strain.
Abstract: Fewer lung adenomas were induced by urethan in BALB/cBy mice than in the A/J or SWR/J mouse strains. When BALB mice were crossed with either of these more sensitive strains the response of the progeny to urethan was most easily explained by a single gene which regulates susceptibility, with the more resistant phenotype behaving as a dominant trait. C56BL/6J mice were more resistant to adenoma induction than were BALB mice; progeny obtained when these two strains were crossed resembled the BALB susceptibility phenotype. As an approach to understanding the mechanism of action of this gene, agents that modulate adenoma initiation and tumor promotion were tested in BALB mice and other strains. The number of adenomas in BALB mice were increased severalfold by multiple urethan injections, which presumably affect initiation, and by the use of butylated o-hydroxytoulene as a promoting agent. Tumor incidence in A-mice was increased 50% by each treatment; neither procedure caused tumors to appear in the resistant DBA/2J, C3H/-21BG, or C57BL/6J strains. No relationship was observed between the strain dependency of the lethal effects of multiple injections of these agents and the relative susceptibilities of these strains to adenoma induction. The role of certain host factors in the regulation of tumor susceptibility was also tested. Homozygosity for the beige (bg) mutation had no effect on tumor numbers in C57 mice, suggesting that natural killer cells, deficient in bg/bg mice, played no major role in determining adenoma susceptibility in this strain. No correlation was found between the susceptibility of various sublines to urethan-induced lung adenoma and the reported relative tumoricidal capacities of the peritoneal macrophages from these sublines.

Journal ArticleDOI
TL;DR: The presence of major histocompatibility antigens on tumor cells and the nature and distribution of mononuclear cellular infiltrates in benign and malignant human breast tumors were studied by the use of monoclonal antibodies and immunoperoxidase techniques on frozen tissue sections.
Abstract: The presence of major histocompatibility antigens [HLA-A,B,C; beta 2 microglobulin (beta 2)m; la-like] on tumor cells and the nature and distribution of mononuclear cellular infiltrates in benign and malignant human breast tumors were studied by the use of monoclonal antibodies and immunoperoxidase techniques on frozen tissue sections. Although all benign tumors expressed HLA-A,B,C or beta 2m, 20 of 53 primary breast cancers did not react with anti-HLA-A,B,C or anti-beta 2m antibodies. Expression of la-like antigens was rarely encountered on tumor cells. The intensity of the inflammatory mononuclear cellular response did not correlate with the expression of HLA-A,B,C or beta 2m by the tumor cells. Most of the mononuclear cells were identified as T-cells. T-cells with a cytotoxic-suppressor phenotype (T8+) were generally the predominant cell type among those found as single cells in the tumor stroma or invading tumor nests. However, infiltration of tumor nests by lymphocytes was infrequently seen and was usually limited to the periphery of the tumor. In contrast, lymphocytes with a helper-inducer phenotype (T4+, Leu-3a+) predominated in the lymphoid aggregates. Anti-Leu-7 (HNK-1) antibody, which reacts with natural killer cells, stained only a few mononuclear cells in the cellular infiltrate in most cases of breast cancer.

Journal ArticleDOI
TL;DR: Positive findings regarding oral contraceptive use and age at birth of first child must be interpreted cautiously pending results of other studies, they suggest that hormonal factors can play a role in the etiology of SSM.
Abstract: 87 women ages 37-74 who resided in King County Washington and who had been diagnosed between July 1976-November 1979 as having cutaneous malignant melanoma were interviewed regarding prior use of estrogen-containing preparations and reproductive history. The responses were compared with those of a random sample of 863 women from the same county. Among the 61 women with superficial spreading melanoma (SSM) use of oral contraceptives (OCs) for 5 years or more was more common than among controls. The estimated relative risks for users of 5-9 and 10 years or more were 2.4 and 3.6 respectively. No differences between cases and controls were noted for OC use of 4 or fewer years. Giving birth to a 1st child after age 30 was also associated with an increased relative risk of SSM. Although the positive findings regarding OC use and age at birth of 1st child must be interpreted cautiously pending results of other studies they suggest that hormonal factors can play a role in SSM etiology. (authors modified)

Journal ArticleDOI
TL;DR: It was concluded that, when orally administered under the conditions of this experiment, potassium bromate was carcinogenic to F344 rats.
Abstract: The carcinogenicity of potassium bromate, a food additive and a neutralizer in permanent waving, was tested by adding it to the drinking water of F344 rats for 110 weeks. Groups of 53 males and 53 females, each, were given solutions of 500 or 250 ppm of potassium bromate or distilled water. A concentration of 500 ppm markedly inhibited an increase of body weight of male rats. The mean survival time was shortest for males given 500 ppm (88.1 +/- 18.1 wk); the survival times of other groups were 101-104 weeks. The percentage survival in week 104 was relatively high in all groups, and it was 77.4% for males and 66.0% for females in the control group. High incidences of renal cell tumors (in males and females given 500 or 250 ppm) and mesotheliomas of the peritoneum (in males given 500 ppm) were observed. The incidences of these tumors in test groups were significantly higher than those in controls (P less than .001). It was concluded that, when orally administered under the conditions of this experiment, potassium bromate was carcinogenic to F344 rats.

Journal ArticleDOI
TL;DR: The increasing risk of lung cancer with number of years licensed and the capacity of certain pesticides to produce neoplasms in laboratory animals suggested that some pesticides may be carcinogenic in humans.
Abstract: The mortality experience of a cohort of 3,827 white men licensed to apply pesticides in Florida was evaluated to investigate health effects associated with chronic exposure to pesticides. Although the overall standardized mortality ratio (SMR) for these structural pest control workers was not significantly elevated (SMR = 103), excess deaths were observed for leukemia, particularly acute myeloid leukemia (3 observed vs. 0.9 expected), and cancers of the brain (SMR = 200) and lung (SMR = 135). The risk of lung cancer rose with the number of years licensed with SMR of 101, 155, and 289 among those licensed for less than 10 years, for 10-19 years, and for 20 years or more, respectively. Ratios of directly adjusted rates showed similar patterns with observed-to-expected ratios of 100, 175, and 186 for the length of licensure categories. Mortality from lung cancer was greater among persons first licensed before age 40 (SMR = 234) than among those first licensed after age 40 (SMR = 115). Although information on tobacco use was not available, the increasing risk of lung cancer with number of years licensed and the capacity of certain pesticides to produce neoplasms in laboratory animals suggested that some pesticides may be carcinogenic in humans.

Journal ArticleDOI
TL;DR: A nutrition survey was done in four Colombian villages situated in the rural area of Nariño, previously identified as exhibiting different levels of risk for gastric cancer and its precursor lesions, which reflected a higher consumption of fava beans in villages with high indices of Gastric cancer risk and a higher Consumption of fresh fruits and vegetables in villages where such indices were lower.
Abstract: A nutrition survey was done in four Colombian villages situated in the rural area of Narino, previously identified as exhibiting different levels of risk for gastric cancer and its precursor lesions. The survey was based on personal visits by trained interviewers to a random sample of families in each village. The major findings of the survey reflected a higher consumption of fava beans in villages with high indices of gastric cancer risk and a higher consumption of fresh fruits and vegetables in villages where such indices were lower. Excessive salt intake and lower potassium intake in villages with a high risk of gastric cancer were suggested, but further work is required to test this preliminary observation. A generally low intake of animal proteins and a high intake of cereals in Narino did not discriminate between villages at different levels of risk to gastric cancer and its precursors.