Showing papers by "International Agency for Research on Cancer published in 1978"
TL;DR: Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma.
Abstract: Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.
557 citations
TL;DR: A linear logistic model used to estimate multiple risk functions in both cohort and case-control studies is adapted for sampling plans wherein each case is matched with R controls and substantially liberalizes current practice.
Abstract: A linear logistic model used to estimate multiple risk functions in both cohort and case-control studies is adapted for sampling plans wherein each case is matched with R controls. The resulting methodology substantially liberalizes current practice by permitting simultaneous analysis of multiple discrete and continuous risk factors. Interactions among risk factors, and between risk factors and matching variables, may be explored. Data from two studies of oesophageal cancer, one conducted among Singapore Chinese and the other on the Caspian littoral of Iran, illustrate the methods.
351 citations
TL;DR: A more than two‐fold reduction in mortality has been observed among women aged 25–59 and there has been a similar decrease in incidence of tumours of stages II, III and IV.
Abstract: A clinic for early detection of cancer of the uterine cervix has been in operation in Iceland since 1964, aimed until recently at the age-group 25-59 More than 85% of women in this age group have been screened at least once Mortality from cancer of the cervix had been rising in Iceland, and continued to rise during the first few years of operation of the screening clinic Since 1970, however, a more than two-fold reduction in mortality has been observed among women aged 25-59 There has been a similar decrease in incidence of tumours of stages II, III and IV Both deaths and advanced tumours are largely confined to women who have never been screened Alternative explanations are considered, but the only tenable explanation of the reduction in mortality is that it is a consequence of the introduction of a comprehensive screening programme
179 citations
TL;DR: Treatment of several human lymphoid cell lines with antisera to human IgM activates the latent EBV genome to give a marked increase in EBV-specific early antigen (EA) and in some cell lines this treatment induces an increase in virus capsid antigen (VCA).
Abstract: EPSTEIN-BARR VIRUS (EBV) is the causative agent of most infectious mononucleosis1 and is also associated with two human tumours, Burkitt's lymphoma (BL)2 and nasopharyngeal carcinoma2. Lymphoid cell lines of B-cell origin have been established from patients with these diseases, and from lymphocytes transformed in vitro by EBV3. In lymphoid cell lines the lytic viral cycle is usually repressed even though the cells carry multiple copies of the EBV genome. These cells therefore provide a valuable model for the study of latent EBV infection. Although EBV is ubiquitous, its association with human malignant disease is to a large extent both ethnically and geographically restricted2 and it is therefore of interest to understand the host factors involved in the regulation of the expression of the latent EBV genome. In infectious mononucleosis, EBV infection is associated not only with a specific anti-EBV antibody2 and T-lymphocyte response4 but also with an increase in nonspecific IgM production5. EBV-infected B lymphocytes produce polyclonal Ig (ref. 6) and the majority of established EBV genome-positive lymphoid cell lines possess surface IgM (ref. 7). We report here that treatment of several human lymphoid cell lines with antisera to human IgM activates the latent EBV genome to give a marked increase in EBV-specific early antigen (EA). Also, in some cell lines this treatment induces an increase in virus capsid antigen (VCA).
176 citations
TL;DR: A cohort of 9,454 patients with infectious mono‐nucleosis, serologically confirmed, was followed up and it was concluded that a positive association exists between infectious mononucleosis and Hodgkin's disease.
Abstract: A cohort of 9,454 patients with infectious mononucleosis, serologically confirmed, was followed up to determine their risk of developing lymphoproliferative diseases. A total of 1,759 patients was identified in Scotland from 1959 to 1971 and 7,695 in Sweden from 1952 to 1970. The cancer cases were identified by matching the list of patients with infectious mononucleosis against a list of patients with lymphoma, nasopharyngeal and colon carcinomas registered through 1972 in Sweden and through 1973 in Scotland. A four-fold increase in risk was found for Hodgkin's disease based on 7 cases observed against 1.8 expected. Most of the excess cases of Hodgkin's disease occurred within three years of the diagnosis of infectious moonucleosis and among females. These results are similar to those of four other cohort studies and it is concluded that a positive association exists between infectious mononucleosis and Hodgkin's disease. Several explanations of this association were evaluated. Firstly, it may be that a very small proportion of persons who are in the course of developing Hodgkin's disease are temporarily misdiagnosed as having infectious mononucleosis. Secondly, infectious mononucleosis may increase the susceptibility to a factor which causes or promotes the development of Hodgkin's disease. Thirdly, infectious mononucleosis and Hodgkin's disease may share a common aetiology. Arguments in favour of, or against, each of these explanations are presented.
128 citations
TL;DR: In this article, substances commonly sucked or chewed in two areas where the incidence of oesophageal cancer is high, the Transkei and north-east Iran, were tested in bacterial mutagenicity assays.
111 citations
TL;DR: The relationship between active hepatitis B and P.H.C.V. seen in African and Asian populations is now seen in a European Caucasian population with different racial, environmental, and dietary circumstances.
107 citations
TL;DR: A prospective investigation of a cohort of 31,453 women confirmed previous findings of the increased risk following higher age at first pregnancy and for nulliparous women.
Abstract: A previous publication has shown that there has been a great increase in the incidence of breast cancer in Iceland. The present study was undertaken to evaluate the importance of known risk factors connected with the reproductive history of the women. In a prospective investigation of a cohort of 31,453 women we confirmed previous findings of the increased risk following higher age at first pregnancy and for nulliparous women. The age at first pregnancy and the proportion of nulliparous women have decreased with time in the Icelandic population so that these factors should have tended to decrease the risk, making the found increase still more important. The effect of parity is that the risk decreases with larger number of children and this effect is independent of the effect of age at first pregnancy. Lower age at menarche increases the breast cancer risk, but the contribution of that factor to the overall risk is negligible.
78 citations
TL;DR: Investigating whether direct or proximate contact between target cells and such mediators of metabolism is necessary for the induction of mutagenesis of mammalian cells and, possibly, also in bacterial systems suggests that such contact is essential.
Abstract: Direct or proximate contact between cells and metabolic activation systems is required for mutagenesis
55 citations
TL;DR: In samples of adult men from two Scandinavian populations with 4-fold differences in colon cancer incidence, a comparison was made of estimated food records over 4 days, defecation habits, mouth-to-anus transit time, and stool weight, suggesting a possible protective role of dietary fiber, unrelated to transit time.
50 citations
TL;DR: The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and should encourage the implementation of extended clinical and field trials.
Abstract: Praziquantel (Embay 8440, Droncit) a new, effective anti-schistosomal drug, was tested in various short-term assays that have shown a predictive value for the detection of potential carcinogens. Indicator organisms S. typhimurium strains, S. pombe, S. cerevisiae, cultured V79 Chinese hamster cells or human heteroploid cells and Drosophila melanogaster were treated with Praziquantel. The induction of reverse and forward mutations, mitotic gene conversions, X-linked recessive lethals, sister-chromatid exchanges and unscheduled DNA-repair synthesis was scored; rodent-liver microsome-, cell- and host-mediated assays were also performed. Hycanthone, another schistosomicide was included as a positive control. The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests (i) confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and (ii) should encourage the implementation of extended clinical and field trials.
TL;DR: Dimethylbenz[a]anthracene and its 3,4, 5,6, 8,9- and 10,11-dihydrodiols have been tested for mutagenicity towards S .
TL;DR: In this paper, the authors proposed a statistical approach for space-time clustering using Pearson curves (e.g. Pearson curves) and the first four moments of the distribution.
Abstract: Mantel proposed a statistic for assessing space-time clustering. He showed how to compute its theoretical expectation and variance and pointed out its asymptotic normality, noting that a simulation approach might be used in insufficiently asymptotic situations. Another approach to this distribution problem is presented by which graduation curves (e.g. Pearson curves) are fitted to the theoretical distribution. This requires the computation of the exact first four moments and the formulae are presented herein. In terms of computer time, this compares favourably with a simulation approach. The analysis of two sets of data confirmed that normality of the test statistic cannot be taken for granted and that a variety of inverse transformations of the time and space data and Knox's method were equally robust.
TL;DR: The hypothesis that alpha-carbon hydroxylation is one mechanism involved in the metabolic activation of N,N-dialkylnitrosamines is supported.
Abstract: A series of N,N-dialkylnitrosamines (alkyl means methyl, ethyl, n-propyl, n-butyl or tert-butyl group) mono-substituted at the α-carbon with an acetoxy group, were tested for their mutagenic action in Salmonella typhimurium TA1530 in the presence or absence of a rat-liver supernatant from 9000 × g. The presumed released of methyl, ethyl, n-butyl and n-propyl carbonium ions from the corresponding α-acetoxy derivatives, either by enzymic cleavage or by non-enzymic hydrolysis of the ester group, caused high mutagenicity in the bacteria. As has been demonstrated for certain α-acetoxy compounds, the mutagenicity of these compounds was inversely related to their half-lives in aqueous media. N-(Acetoxy)methyl-N-tert-butylnitrosamine and a β-acetoxy derivative of N,N-diethylnitrosamine were not mutagenic either in the presence or in the absence of hydrolysing rat-liver enzymes. These results support the hypothesis that α-carbon hydroxylation is one mechanism involved in the metabolic activation of N,N-dialkylnitorsamines.
TL;DR: It was concluded that inhibition by lecithin may most likely occur early at a time following binding of the mitogen but before the cells are committed to cellular division and it seems that the plasma membrane might be a likely site of action of the lipid.
TL;DR: Results obtained indicate that the 9,10-dihydrodiol derived from 3-methylcholanthrene is involved, presumably following conversion into the corresponding vicinal diol-epoxide, 9, 10- dihydro-9-10-Dihydroxy-3- methylcholthrene 7,8-oxide, in the metabolic activation of this carcinogenic polycyclic hydrocarbon.
TL;DR: Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma, nasopharyngeal carcinoma, or normal persons.
Abstract: Detection of the Epstein-Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti-IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine.
TL;DR: The chromatography of alpha‐fetoprotein (AFP) containing sera on concanavalin A‐Sepharose 4 B immunoadsorbant yields two fractions, one which does and the other which does not bind the Con A.
Abstract: The chromatography of alpha-fetoprotein (AFP) containing sera on concanavalin A-Sepharose 4 B immunoadsorbant (Con A) yields two fractions, one which does and the other which does not bind the Con A. It is thus possible to calculate for various specimens the ratios
Mean ratios of three categories of sera whose AFP titres varied between 14,000 and 430,000 IU/ml were the following: eight cord sera, m = 19.1 ± 4.2%; seven primary liver carcinoma sera (PLC), m = 15.9 ± 2.4%; three teratoblastoma sera, m = 37.5 ± 5.5%. The comparison of mean values by the Wilcoxon test indicated that there were statistically significant differences (p<0.05) between cord sera and teratoblastoma sera on the one hand, and between PLC and teratoblastoma sera on the other hand. It was also found that the ratios did not depend upon levels of AFP in sera. Variations of serum glycoproteins such as those reported in cancer patients are unlikely to account for these differences, especially since they are of much smaller magnitude than those achieved in in vitro experiments. Establishing the existence of patterns of heterogeneity of AFP linked to the origin of serum specimens will however require, in order to eliminate possible interferences by other glycoproteins, the use of purified AFPs. Should the existence of such patterns be confirmed, it will be interesting to see if they are related to differences such as those recently reported between fetal and tumour AFP when inhibition of lymphocyte stimulation was used.
TL;DR: Evidence indicates fat and meat may increase bile secretion and thus carcinogenic products that act on the colon and rectum, however, multifactorial causes seem involved.
Abstract: Diet may influence human carcinogenesis by: carcinogens in food or drink that act directly or indirectly; increased delivery of carcinogens to epithelial tissues by acting as solvents; metabolic activation or inactivation, usually by enzymes, of carcinogens due to induction by specific diet components; carcinogen formation in the body resulting from dietary substrates or internal secretions; indirect effects on host metabolism, such as obesity; protective physical effects, such as dietary fiber; and inhibition of premalignant lesions. Colon cancer incidence is highest in western Europe, North America, and Australia, and geographic differences suggest environmental causal factors. Evidence indicates fat and meat may increase bile secretion and thus carcinogenic products that act on the colon and rectum. However, multifactorial causes seem involved.
TL;DR: The existence of two alpha‐fetoproteins, one which does and the other which does not bind the concanavalin A, was confirmed by affinity chromatography and the slopes of dose‐response curves obtained by the radioimmunoassay with twelve antisera were steeper for binding fractions but differences with non‐binding alpha‐ Fetoprotein were not significant.
Abstract: The existence of two alpha-fetoproteins, one which does and the other which does not bind the concanavalin A, was confirmed by affinity chromatography. The non-binding alpha-fetoprotein represented about 2.3% of the total and the binding alpha-fetoprotein was constituted by a series of fractions with different avidities. The electrophoretic mobility of fractions which bound was greater and this was due to differences in charge, not in molecular weight; on the other hand binding and non-binding alpha-fetoproteins were identical when compared by gel diffusion; the slopes of dose-response curves obtained by the radioimmunoassay with twelve antisera were steeper for binding fractions but differences with non-binding alpha-fetoprotein were not significant. Alpha-mannopyranosyl or sterically identical determinants of alpha-fetoprotein through which the binding to the concanavalin A occurs are different from alpha-fetoprotein antigenic sites; both can be weakly masked by sialic acid.
01 Jan 1978
01 Jan 1978
TL;DR: The role of mycotoxins in human disease is discussed in this article, where the authors stress the necessity for co-operation between chemists, veterinarians, mycologists and physicians in the elucidation of the role of the mycotoxin in human diseases.
Abstract: The general background of the role of mycotoxins in human disease is briefly reviewed. The clinical assessment of individual cases of mycotoxicosis and of epidemics is considered. The acute effects of the ingestion of the aflatoxins and the part that long term exposure may play in human disease, notably cancer, are examined. The necessity for co-operation between chemists, veterinarians, mycologists and physicians in the elucidation of the role of the mycotoxins in human disease is stressed.
01 Jan 1978
TL;DR: There seems no reason why PAH should not be controlled either directly in the food or in the smoke additive, as good methodology exists for the determination of PAH and the technology exists to limit their content in smoke additives.
Abstract: Although smoking of foods has been long established as a method for its preservation, the possibility that smoking can introduce compounds which may be carcinogenic to man poses problems for legislation relating to public health. While evidence from industrial exposures which correlate cancer incidence and benzo a pyrene intake is strong, it must be recognized that although they have not been measured, other chemical carcinogens might be involved in the smoking of food. The most important example here would be N-nitroso compounds. Since PAH are ubiquitous in our environment a major problem is to take decisions on levels which can be tolerated. Present evidence suggests that PAH contamination of green vegetables mainly from traffic fumes is likely to be at least as great as the contamination of smoked food where modern technology is employed. Other factors which may affect the situation are co- and anti-carcinogenic factors which may be associated with different diets of which little is at present known. Although there is generally a reluctance to legislate specifically for carcinogens, a number of nations have introduced legislation to limit aflatoxin content in foods. As good methodology exists for the determination of PAH and the technology exists to limit their content in smoke additives, there seems no reason why PAH should not be controlled either directly in the food or in the smoke additive.
01 Jan 1978
TL;DR: In this paper, different biological end-points have been proposed for the various short-term tests designed to detect potential carcinogens: DNA-binding of carcinogens or their metabolites, mutagenicity, induction of DNA repair, enhancement of biphenyl 2-hydroxylase, degranulation of rat liver endoplasmic reticulum, cytogenetic alterations and in vitro cell transformation.
Abstract: The hepatocarcinogenicity of aflatoxins and sterigmatocystin in a variety of animal species and probably, in man, has led to a search for other carcinogenic fungus derived products. Different biological end-points have been proposed for the various short-term tests designed to detect potential carcinogens: DNA-binding of carcinogens or their metabolites, mutagenicity, induction of DNA repair, enhancement of biphenyl 2-hydroxylase, degranulation of rat liver endoplasmic reticulum, cytogenetic alterations and in vitro cell transformation. Based on recent data in the literature, these short-term testing procedures, which appear to be useful for the detection of potential carcinogens and mutagens, and which can be used in the studies of the mechanism of action of chemical carcinogens and mutagens, are limited in that some of the factors which determine the process of cancer development cannot so far be duplicated. Positive results in short-term tests cannot automatically be taken to imply a definite carcinogenic activity in man. Consequently, various short-term tests can be utilised to trace carcinogens or mutagens in man's environment or for prescreening those compounds to be tested for carcinogenic action in animals.