Showing papers by "International Agency for Research on Cancer published in 1975"

Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains.

Abstract: Exposure of S. typhimurium strains TA 1530, TA 1535 and G-46 to vinyl chloride increased the number of His+ revertants/plate 16, 12 or 5 times over the spontaneous mutation rate. After 6 h of exposure to vinyl chloride, the mutagenic response for TA 1530 strain was enhanced 7-, 4- or 5-fold when fortified postmitochondrial liver fractions from humans, rats or mice were added. The enzyme-mediated vinyl chloride mutagenicity was dependent on an NADPH generating system and the enzyme activity was localized in a liver microsomal fraction; 9,000 times g liver supernatant was three times more active than microsomes, while liver cytosol or alcohol dehydrogenase did not affect the mutagenicity. Phenobarbitone pretreatment of rats and mice increased the mutagenic response by up to 15-40 percent as compared to untreated controls. The relative mutagenic activities of VCM, taking the value from mouse liver as 100, for TA 1530 strain mediated by 9,000 times g tissue fractions were: rat liver, 80; mouse and rat kidney, 20 and 16; mouse and rat lung, less than 7; human liver (from four biopsy specimens) 170, 64, 70 and 46. Chloroacetaldehyde and chloroacetic acid, a urinary metabolite of VCM, showed toxic effects, while chloroethanol was weakly mutagenic for TA 1530 strain.

Nasopharyngeal carcinoma. X. Presence of epstein-barr genomes in separated epithelial cells of tumours in patients from Singapore, Tunisia and Kenya.

Abstract: Nasopharyngeal carcinoma (NPC) biopsies from Singapore, Tunisia and Kenya were compared, before and after separation of epithelial and lymphoid cells, for their EBV-DNA content, using the cellular DNA-EBV-cRNA hybridization test. In all instances where successful separation of the two cell types was achieved, epithelial tumour cells showed a higher EBV-DNA content than lymphoid cells or tumour before cell separation. It is, therefore, suggested that EBV-DNA is mostly limited to epithelial cells. No significant difference was observed between NPC tumours originating from various geographical areas.

Tissue-mediated mutagenicity of vinylidene chloride and 2-chlorobutadiene in Salmonella typhimurium.

Abstract: CHLORINATED hydrocarbons, such as vinyl chloride or vinylidene chloride (1,1-dichloroethylene), are produced in large quantities and are present in the environment1. Recently, vinyl chloride monomer has been shown to be carcinogenic in animals and man2–4 and mutagenic in microbial systems5–7. Vinylidene chloride (VDC), a structurally related substance and co-polymer of vinyl chloride, is used in the manufacture of plastics8; it could also occur as a decomposition product of 1,1,1-trichloroethane1. Another chemically related compound, 2-chlorobutadiene (chloroprene), has been used in the manufacture of synthetic rubber since 1930.

Mutation induction in chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2-chloroacetaldehyde

Abstract: Chloroethylene oxide and 2-chloroacetaldehyde, two possibly carcinogenic metabolities of vinyl chloride in mammals, caused a dose-dependent induction of 8-azaguanine- and ouabain-resistant mutants in Chinese hamster V79 cells in vitro. Up to one-hundred-fold higher concentrations of 2-chloroethanol or monochloroacetic acid, a urinary vinyl chloride metabolite in rats and man, were inactive.

Production of epithelial and mesenchymal tumours with rat liver cells transformed in vitro.

Abstract: Epithelial-like cells originating from the livers of 10-day and 8-week-old BD rats were established in culture. The cells were treated in vitro for 1 or 4 weeks with dimethylnitrosamine (DMN) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Although some structural changes were observed in treated cells, it was not possible to score for morphological transformation in vitro. Newborn syngeneic rats were injected with 1.5-2 times 10(6) treated or 1.5-5 times 10(6) control cells at various times up to 38 weeks from the beginning of treatment with the carcinogen. Following the injection of DMN-treated cells, a total of 32 of the 42 injected rat developed tumours, of which 17 were epithelial, 10 carcinosarcomas and 5 fibrosarcomas. Following the injection of the MNNG-treated cells into 61 rats, a total of 30 tumours were observed, including 8 carcinomas, 9 carcinosarcomas and 13 fibroscarcomas. Tumours, mainly of the mesenchymal type, were also observed in rats inoculated with control cells but at a lower frequency. The observation observed in rats inoculated with control cells but at a lower frequency. The observation of mesenchymal tumours is attributed to the presence of a mixed population of epithelial and mesenchymal cells in the orginal culture.

Nasopharyngeal carcinoma. IX. Antibodies to EBNA and correlation with response to other EBV antigens in Chinese patients

Abstract: Ninety-five sera from Chinese NPC patients in different stages of the disease, 38 sera from Chinese patients with other cancers, and 50 normal Chinese sera, were titrated for EBNA, VCA, EA and complement-fixing (CF/S) EBV-specific antibodies The geometric mean (GMT) EBNA antibody titre of patients with NPC at stage I was found to be four times higher than that of normal individuals and increased in parallel with clinical deterioration Antibody titres against EBNA did not correlate with either VCA or EA antibodies but, in general, correlated with CF/S antibodies EA antibodies correlated relatively well with VCA antibodies and discriminated better than EBNA titre between NPC at stage I and controls

The relationship between nasopharyngeal carcinoma and the HL-A system among Tunisians.

Abstract: Previous reports have demonstrated an association between the HL-A system and risk for nasopharyngeal carcinoma among the Chinese in Singapore. The present paper describes an investigation of HL-A profiles among NPC cases and non-NPC controls from Tunisia, to determine whether a similar association occurs in a different ethnic group. A total of 109 NPC cases and 84 controls were typed. At the second HL-A locus the results were similar to those found in Singapore, but the effect was less marked and did not reach high statistical significance. At the first HL-A locus, no association between A2 and NPC was found, in contrast to the Singapore results.

The occurrence of tumours in F1, F2 and F3 descendants of bd rats exposed to N-nitrosomethylurea during pregnancy.

Abstract: N-nitrosomethylurea (NMU) was administered once IP at a dose of 20 mg/kg to BD female rats on the 18th day of pregnancy. The first generation descendants (F1) were mated to produce a second generation (F2), which were then mated to produce a third generation (F3). While F1 rats were exposed directly to NMU during intrauterine life, it can be reasonably excluded that F2 and F3 descendants were exposed to NMU or its metabolites. F2 and F3 rats received no other treatment and untreated rats served as controls. Kidney and nervous-tissue tumours were observed in F1 descendants and, with a lower incidence, in F2 descendants. In F3 rats, tumours of nervous tissue, but not of kidneys, were observed. These results confirm previous observations that exposure to a carcinogen during prenatal life results in an increased cancer risk which may persist for more than one generation.

Lymphoblastoid transformation and kinetics of appearance of viral nuclear antigen (EBNA) in cord-blood lymphocytes infected by Epstein-Barr Virus (EBV).

Abstract: Human cord-blood lymphocytes were infected with B95.8 Epstein-Barr virus (EBV) before and after separation into B- and T-cell populations. Lymphoblastoid cells exhibiting B-cell characteristics appeared after 2 to 3 days of culture in the total population and in the separated B-cell subpopulation but not in the T-cell subpopulation. EBV nuclear antigen (EBNA) was detected concurrently with the appearance of lymphoblastoid cells. The proportion of EBNA-positive cells corresponded to that of lymphoblastoid cells, and reached 50% after 4 days. EBNA was present only in cells with B-cell markers. These observations indicate that only B-cells are susceptible to EBV infection, that the transformation occurs within a few days and that EBNA is a valid early marker for susceptibility to EBV transformation.

Cancer of the Oesophagus in Brittany: An Incidence Study in Ille-et-Vilaine

Abstract: Mortality from cancer of the oesophagus is known to be high in Brittany and Normandy. A morbidity survey was initiated to confirm this finding. A registry was set up in Rennes for the departement of Ille-et-Vilaine. In the course of six years (1968-73) 718 cases were entered, 669 males and 49 females; the annual incidence rate for males is 29-4 per 100,000, one of the highest ever described. Most tumors are in the middle third of the oesophagus (49 per cent); 33 per cent are in the lower third. Most tumors were squamous cell carcinomas; 7 per cent were adenocarcinomas. There is an area of high endemicity in the rural areas of the north of Ille-et-Vilaine with rates reaching 60 per 100,000. The relationship with drinking habits is currently being investigated.

Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks.

Abstract: Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

Organochlorine compounds in the general population of the seventies and some of their biological effects (in man and animals

Abstract: The interaction of an organism and its environment is determined, to a significant degree, by the composition of the environment and the biochemical individuality of the given organism. A characteristic of the living organism is to carry the foreign compounds which enter them through continuous cycles of activity like their own constituents. Some of the compounds of the environment accumulate to some extent in the animal body. This storage constitutes a dynamic process. At a certain storage level, effects on the metabolism of normal constituents of the animal body, on the genetical make-up, and on its defence mechanisms (detoxication processes, neuro-endocrine, and immunologic processes) are observed. This paper reports on the size of Organochlorine Insecticides and Poly-chlorinated Biphenyls storage in the human general population in the seventies and some of the biological effects of these compounds on humans and experimental animals.

In vitro immunological studies on east african cancer patients. III. Spontaneous rosette formation by cells from Burkitt lymphoma biopsies.

Abstract: Spontaneous rosette formation was observed in eight out of nine Burkitt lymphoma biopsies. These were examined fresh and/or after culture in vitro for up to 48 h. The percentage of rosettes varied from 3.7% to 38%. There was a tendency for the percentage of rosettes to increase with time in tissue culture. It is suggested that the rosette-forming cells are T-lymphocytes infiltrating the tumour and functioning as a host defence mechanism against the proliferating tumour cells.

In vitro immunological studies on East African cancer patients. II. Increased sensitivity of blood lymphocytes from untreated Burkitt lymphoma patients to inhibition of spontaneous rosette formation.

Abstract: Frozen aliquots of peripheral blood mononuclear cells from patients with Burkitt's lymphoma (BL) at various stages of the disease have been compared with samples from East African children who were healthy or who suffered from non-malignant disorders. Using the sheep-cell rosette test (which is believed to identify T-lymphocytes), we found a significant reduction in the proportion of rosette-forming cells (RFC) in the samples from untreated BL patients. After induction of remission the difference between BL patients and controls was abolished. Rosette formation was more readily inhibited by anti-lymphocyte globulin (ALG) in samples from untreated BL patients than in controls. On induction of remission the rosette inhibition curve shifted towards the control values. The findings are compatible with the presence, in untreated BL, of a circulating factor which impairs the capacity of T-lymphocytes to form rosettes with sheep erythrocytes. It remains to be established whether the functional capacity of T-cells to protect the host against tumour proliferation is also impaired.

Cancer of asians in kenya.

Abstract: The frequency of various cancers among Indian immigrants in Kenya was compared to corresponding data among native Africans and Indians in the regions of India from which most of the studied population originally migrated. The Kenyan Indians do not have the cancer pattern of their home country nor do they have the cancer pattern of indigenous Africans. They have instead, like Europeans and North Americans, a higher risk of cancer of the lung, breast and the large intestine. It is suggested that this is related to enbironmental factors and variations in living habits.

The effect of hormone induced stress upon the extent of alkylation of rat liver nucleic acids by N-methyl-N-nitrosourea

Abstract: An examination was made of the effect of treatment with methylating agents of varying carcinogenic potency and with stress inducing hormones upon DNA synthesis in the resting liver of the rat. With the methylating agents an early stimulation of DNA synthesis was observed, but this was depressed below the control levels at later times and with higher doses; hormone administration also resulted in a depression of DNA synthesis but, without any initial stimulation at the dosage employed. Under conditions of induced stress it was found that the extent of reaction of N-methyl-N-nitrosourea with cellular macromolecules was enhanced. This appeared to be a general effect upon the liver cell since both DNA and rRNA were affected in a similar manner.

Lung cancer and smoking in Danish women.

Abstract: In most developed countries, including Denmark, cancer of the lung is the most frequent malignant disease among men, whereas the problem is less among women. Examination of Danish mortality data for the period 1931 to 1972 reveals a 5-fold increase in female rates as opposed to a 16-fold increase in male rates. Since about 1960 female rates have, however, increased faster than male rates with a consequent decline in the male-famale ratio. It is demonstrated that more recent female birth-cohorts have higher mortality rates than the older ones. The increasing mortality from lung cancer among more recent female cohorts is shown to parallel increasing proportions of smokers in these cohorts. Further data are presented to indicate that not only is smoking more widespread among young than among old women, but the proportion of cigarette smokers among all smokers falls from 98% in the youngest to 33% in the oldest agegroup. No causal relationship between smoking and lung cancer can be claimed from the evidence presented. The present findings are, however, what would be expected if cigarette-smoking were an aetiological factor in female lung cancer.

Do viruses cause cancer in man

Abstract: Many factors are involved in the in duction of animal and human cancer: ionizing radiation, chemical carcino gens, age, hormone balance and genetic constitution of the host. In addition, viruses are known to cause tumors in animals such as frogs, fowl, rodents, cats, cows and monkeys, and it is im probable that cancer in man has a fun damentally different etiology. However, it is unlikely that evidence of the viral etiology of human cancer will ever fully satisfy Koch's postu lates. These include that: (I) the micro-organism must be observed in most cases of the disease; (2) it must be isolated and grown in pure culture; (3) the pure culture must, when inocu lated into a susceptible animal, repro duce the disease; and (4) the micro organism must be observed in, and recovered from, the experimentally diseased animal. Thus, supporting evi dence that viruses cause several human cancers is largely circumstantial and hasbeengatheredinseveralways.One line of attack is to search for virus particles, viral precursors in the form of antigens, and virus-specific nucleic acids in human tumor biopsy samples and cultured tumor cells. Passenger and contaminant viruses should be rig orously eliminated before any agent can