Bg. Lake et al., USE OF PRECISION-CUT LIVER SLICES TO EVALUATE SPECIES-DIFFERENCES IN 2-ACETYLAMINOFLUORENE-INDUCED UNSCHEDULED DNA-SYNTHESIS, Toxicology and applied pharmacology, 138(2), 1996, pp. 231-241
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.