Development and utilization of primary hepatocyte culture systems to evaluate metabolism, DNA binding, and DNA repair of xenobiotics.
The use of isolated hepatocytes as an approach to evaluate hepatotoxic and hepatocarcinogenic compounds and investigate mechanisms by which chemicals induce liver lesions is well established. This review discusses techniques developed in the author's laboratory describing (1) isolation and primary culture of rodent hepatocytes detailing methods which are optimal for obtaining large numbers of viable cells, (2) DNA damage induced by physical and chemical agents in rodent hepatocytes measured as unscheduled DNA synthesis, and (3) metabolic activation of model hepatocarcinogens, their binding to DNA, and identification of individual adducts thought to be responsible for induction of DNA repair.
Casciano
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DA
National Center for Toxicological Research, Division of Genetic and Reproductive Toxicology Jefferson, Arkansas 72079, USA.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D004260:DNA Repair; D015870:Gene Expression; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
D018736:DNA Adducts; D015262:Xenobiotics; D004247:DNA