The search for relevant short term bioassays for chemical carcinogens: the tribulation of a modern Sisyphus.
Based on a good correlation between carcinogenicity and mutagenic activity several rapid microbial bioassays for chemical carcinogens have been recently developed. We would like to suggest, that these microbial tests should be followed by bioassays using cultured human cells of the "average" man, and of persons with elevated cancer risk or increased susceptibility to carcinogenic agents. The main objective of using DNA repair (unscheduled uptake of 3HTdR) and DNA fragmentation (shift in sedimentation profiles) of cultured human cells was to design a test system that can simulate conditions found in man and thus provide information relevant to the human population. A trial on 98 different carcinogens, precarcinogens and noncarcinogens showed the suitability of DNA repair synthesis as a rapid, economic and relevant assay for detection of chemical carcinogens. To check the adaptability of DNA repair synthesis of human cells as a bioassay for chemical carcinogens we examined carcinogenic nitrosation products which are formed from the interaction of nitrite and nitrosatable compounds, carcinogenic or mutagenic photosensitizing chemicals, and the effect of complex interactions. Organotropic carcinogens can be detected by measuring DNA fragmentation and DNA repair in various target organs following the in vivo application of chemical carcinogens. The pros and cons of several bioassays and their usefulness in judging a carcinogenic or mutagenic hazard to human populations is discussed.
D000818:Animals; D001419:Bacteria; D001681:Biological Assay / Q000379:methods; D002274:Carcinogens, Environmental; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002842:Chromatids / Q000502:physiology; D002869:Chromosome Aberrations; D003434:Crossing Over, Genetic; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004347:Drug Interactions; D005796:Genes / Q000187:drug effects; D006801:Humans; D007181:Inclusion Bodies, Viral; D051379:Mice; D009153:Mutagens; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced*; D009603:Nitroso Compounds / Q000096:biosynthesis; D010787:Photosensitivity Disorders / Q000139:chemically induced; D014779:Virus Replication; D014780:Viruses / Q000187:drug effects
D002274:Carcinogens, Environmental; D009153:Mutagens; D009603:Nitroso Compounds; D004247:DNA