[Ecology, demography and malignant neoplasms in St.Petersburg].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to V V Khudoleĭ.
Explore the source record for details and available documents.
Environmental oncology is a discipline concerned with studies of multi-aspect relationships between environment and living organisms exposed to the modifying influence of carcinogenic agents. It also deals with general biological regularities involved in neoplasm development as well as their prevention in different species including man, animals and plants. Various investigations conducted at the Laboratory and supported with Russian and foreign grants (1991-1996) are briefly discussed. Among them are biotesting environmental carcinogens (aminoanthraquinons, by-products of drinking water chlorination, development of new testing systems and objects of detection involved in identification of genotoxic substances (criteria for formation of short-term test batteries and evaluation of perspectives, methods and results), investigation of xenobiotic metabolic activation (enzyme imprinting in adult animals), search for anticarcinogens (classification of carcinogenesis inhibitors, development of testing systems for modifiers selection), and establishing environment-related regularities of tumor growth. Vistas in environmental oncology development are discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The problems of anticarcinogenesis are discussed in the context of mechanistic approaches and the well-known mechanisms of multistage carcinogenesis. Various events at extra- and intracellular levels are involved in mutagenesis and carcinogenesis. The most promising candidates for suppression of chemical carcinogenesis are some nitrosation modifiers, dietary sorbents, metabolic activation modulators, reactive metabolite trappers, repair inducers, gene expression inhibitors, etc. Short-term tests for mutagenicity are more preferable for screening potential anticarcinogenic agents. The bioassays for anticarcinogenesis should be assessed for sensitivity, specificity and predictability and the genetic profiles of the antimutagenic activity of the modifiers analysed.
Explore the source record for details and available documents.
An inductor of a system of multifunctional monooxygenases, the sovol, being applied to hepatectomized adult rats, produced an enzymatic imprinting, which was expressed in a long-term increase in the aryl hydrocarbon hydroxylase, 7-ethoxycoumarin-deethylase and amidopyrine-N-demethylase activities, as well as in the metabolic activation of benzo (a)-pyrene by the liver S9-fraction in the Salmonella/microsome assay. The phenomena of enzymatic imprinting in adult animals, primarily described, is a reflection of response universality of proliferative cells upon inductors action.
Explore the source record for details and available documents.
A well-known inductor of a system of multifunctional monooxygenases, the arochlor 1254, being applied to one-day rats produced an imprinting effect which was expressed in a strong and long-term increase in the metabolic activation of benzo(a)pyrene by the liver S9-fraction in the Salmonella/microsome test, as well as in the arylhydrocarbonhydroxylase activity. The imprinting was not revealed when the inductor was applied on the 9th day as well as it was not revealed for 2-acetylaminofluorene in the liver, or benzo(a)pyrene and 2-acetylaminofluorene in the kidneys, independently of the period of application.
Explore the source record for details and available documents.
Dichlorobromomethane (DCMB) and dibromochloromethane (DBCM) isolated from chlorinated drinking water were tested for toxicity, mutagenicity and carcinogenicity. Both agents proved mutagenic in a "dessicator" modification of the Ames test using Salmonella typhimurium TA98 and TA100 in the presence of exogenous metabolic activation. In aquarium Danio rerio fish tests, LD50/30 was 250 mg/l for both compounds. Both agents induced hepatocellular carcinoma in fish: DCMB--in 11 out of 29 animals (at 16.5 weeks) and DBCM--in 3 out of 16 (at 26.5 weeks). These data merit further investigation of the agents' carcinogenicity in chronic experiments in rodents.
Explore the source record for details and available documents.
Current investigations of modifications of metabolic activation of carcinogens by the environmental chemical factors which are able to induce or inhibit the metabolic activation are reviewed. From the standpoint of ecological oncology the most promising are the following trends: 1) modelling under experimental conditions of integral ecosystems including the complex of living organisms, environmental carcinogens, and factors which modify their biotransformation; 2) study of the imprinting effectors of metabolism modifiers; 3) detection in the environment of modifiers of metabolic activation of carcinogens. The comprehensive oncological-ecological studies of chemicals which influence different pathways of carcinogen metabolism are very important for both primary prevention of cancer and the environmental protection.
Metabolic activation of procarcinogenic 2-acetyl-amino-fluorene, benzo(a)pyrene, aflatoxin B1 and N-nitrosodimethylamine by various tissues of embryonal and newborn rats was studied with the Salmonella/microsome assay. Bioactivation by fetal tissues was shown to be significantly lower than with newborn rat tissues. When aroclor was given to pregnant females a decrease in metabolic activation was observed. This phenomenon was interpreted as a paradoxical effect. Treatment with aroclor of newborns led to a significant increase in biotransformation of all the compounds tested in the liver and after benzo(a)pyrene--in the kidney, and N-nitrosodimethylamine--in the lung.
Explore the source record for details and available documents.
The commercial mixture of polychlorinated biphenyls (Sovol) studied by biochemical and immunochemical methods was found to be an inducer of a wide range of cytochrome P-450 isoenzymes. The induced enzymes activated in the Ames test a series of procarcinogens differing both in structure and in target organs: benz(a)pyrene, 3-methylcholanthrene, nitrosomorpholine, dimethylnitrosamine, aflatoxin B1, orthoaminoazotoluene, 2-acetylaminofluorene, cyclophosphamide and benzidine. According to the parameters the studied Sovol is similar to Aroclor 1254 and may be recommended to be used as an inducer of microsomal enzymes in routine tests for carcinogen screening.
Aquarium fishes Danio rerio and Poecilia reticulata are recommended as test-objects for testing carcinogenic chemical agents. 30 compounds were tested for their action on these objects. The analysis of the incidence of induced tumors, period of their appearance and Iball index shows high sensitivity of the aquarium fishes to the carcinogenic action. Data are presented on the dynamics of experimental carcinogenesis, morphology of induced tumours, as well as on modifications of carcinogenesis (the role of environmental temperature, age, dose, exposition, etc.). Advantages and limitations of the "fish model" are compared with those found in the experiments carried on mammals.
One-hundred and six chemical compounds were tested in Ames test with bacteria Salmonella typhimurium. Eight different strains (mainly, TA98 and TA100) were used. Liver S9 from Aroclor-treated rats was employed for metabolic activation. In group I comprising 51 compounds with sufficient evidence of carcinogenicity for animals, 45 were mutagenic while 6 (urethane, 1,2-dimethylhydrazine, DDT, chlorophorm, 1,4-dioxane and carbon tetrachloride) were not. In group 2 (27 noncarcinogenic compounds), 22 agents failed to exhibit mutagenicity whereas 5 (acrolein, styrene-oxide, acridine orange, I-naphthylamine and dichlormethane) revealed such activity. In groups 1 and 2, the sensitivity was 88.2, specificity--81.5 and predictive value--90%. In group 3 consisting of 28 agents used in chemical, pharmaceutical and food industries but not yet tested for mutagenicity and for the carcinogenicity of which no conclusive data are available, seven appeared to be mutagens (1-aminoanthraquinone, 2-aminoanthraquinone, 1-amino-4-chloranthraquinone, based blue, dinitrochlorbenzene, nitrosodiphenylamine and 2,3,5-trinitronaphthalene).