Genotoxicity of carcinogens in human hepatocytes: application in hazard assessment.
Evaluation of chemical genotoxicity has been used in assessing human cancer hazard, based on the observation that most human carcinogens are known to be DNA-reactive. The availability of data on the DNA-reactivity of compounds in metabolically competent human cells would assist hazard assessment by providing direct information of human genotoxicity. To evaluate the reliability of human hepatocytes for this purpose, the induction of DNA repair by DNA-reactive carcinogens of several structural classes and related noncarcinogens was studied. All the carcinogens elicited DNA repair synthesis, whereas the noncarcinogens did not. These studies provide additional support for the use of human hepatocytes in a DNA repair test in the investigation of genotoxicity. The demonstration of genotoxicity in human cells is suggested to provide important information for hazard assessment.
McQueen
C A
CA
American Health Foundation, Valhalla, New York 10595.
Way
B M
BM
Williams
G M
GM
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000328:Adult; D001345:Autoradiography; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005449:Fluorenes / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
D002273:Carcinogens; D005449:Fluorenes; D001564:Benzo(a)pyrene; C012177:2-aminofluorene; D015073:2-Acetylaminofluorene