Effect of some cooked food mutagens on unscheduled DNA synthesis in cultured precision-cut rat, mouse and human liver slices

Precision-cut liver slices were prepared from male Fischer 344 rats, female CDF1 mice and humans (both male and female subjects). Liver slices were cultured for 24 hr in medium containing [H-3]thymidine and either PhIP, IQ, MeIQ, MeIQ(x), Glu-P-1 or Trp-P-1, and then processed for autoradiographic evaluation of unscheduled DNA synthesis (UDS). All six cooked food mutagens examined produced concentration-dependent increases in UDS in human liver slices. PhIP was the most potent compound examined, followed by MeIQ(x), IQ and then MeIQ, Glu-P-1 and Trp-P-1. Significant increases in UDS were observed with PhIP, IQ and MeIQ(x) at concentrations as low as 5 mu M in the culture medium. The same rank order of potency was not apparent in either rat or mouse liver slices. In rat liver slices only MeIQ significantly induced UDS, although positive results were obtained with two other genotoxins, namely 2-acetylaminofluorene and aflatoxin B-1. Apart from MeIQ(x), all the cooked fi,od mutagens produced significant increases in UDS in mouse liver slices. This study demonstrates the usefulness of precision-cut liver slices to evaluate species differences in xenobiotic-induced genotoxicity. Both marked compound and species differences in induction of UDS were observed. The data provide further evidence that dietary cooked food mutagens are potential human carcinogens. (C) Crown Copyright 1998 Published by Elsevier Science Ltd. All lights reserved.