Primary human and rat hepatocytes in genotoxicity assessment.
Primary cultures of human hepatocytes obtained from liver fragments discarded during prescribed surgery represent a reliable experimental model that provides direct information on the genotoxic effects caused by parent chemicals and their reactive metabolites. A comparison between data so far obtained with the DNA repair induction (UDS) test in human and rat liver cells is presented. Fourteen of the 44 compounds tested were inactive in both species; the man/rat ratio of the 30 active compounds ranged from 0.21 to 3.14. Chloramphenicol induced UDS only in human hepatocytes, while cimetidine, tripelennamine and four n-alkanals caused DNA repair only in rat cells. Three synthetic progestins induced UDS in female, but not in male rats, while they were positive in human cells of donors of both genders. Primary human hepatocytes would seem to be an important model in the study of differences in species sensitivity to xenobiotics.
Martelli
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Department of Internal Medicine, University of Genoa, Italy.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity
D002273:Carcinogens; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate