USE OF PRECISION-CUT LIVER SLICES TO EVALUATE SPECIES-DIFFERENCES IN 2-ACETYLAMINOFLUORENE-INDUCED UNSCHEDULED DNA-SYNTHESIS

Precision-cut liver slices were prepared from male Sprague-Dawley rats (pretreated with or without Aroclor 1254), male Dunkin-Hartley guinea pigs, male cynomolgus monkeys, and humans, Liver slices were cultured for 24 hr using a dynamic organ culture system in medium containing [ H-3]thymidine and 2-acetylaminofluorene (2-AAF), aflatoxin B-1 (AFB(1) ), or 6-aminochrysene (6-AC), The liver slices were then harvested and processed fbr autoradiographic evaluation of unscheduled DNA synthesi s (UDS), All three genotoxins induced UDS in liver slices from untreat ed and Aroclor 1254-treated rats. In human liver slices 2-AAF produced a concentration-dependent induction of UDS and at the highest concent ration examined 2-AAF also induced UDS in guinea pig liver slices. How ever, 2-AAF did not induce UDS in cynomolgus monkey liver slices, alth ough both AFB(1) and 6-AC induced UDS in liver slices from this specie s as well as from guinea pigs and humans, The inability of 2-AAF to in duce UDS in cynomolgus monkey liver slices appears to be at least part ially due to the absence of hepatic CYP1A2 in this species, Precision- cut Liver slices appear to be a useful alternative to primary hepatocy te cultures for studies of xenobiotic-induced genotoxicity employing t he UDS technique. As shown by this study they may also be employed to evaluate species differences in xenobiotic-induced genotoxicity. (C) 1 996 Academic Press, Inc.