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, f emale CDF1 mice and humans (both male and female subjects). Liver slic es were cultured for 24 hr in medium containing [H-3]thymidine and eit her PhIP, IQ, MeIQ, MeIQ(x), Glu-P-1 or Trp-P-1, and then processed fo r autoradiographic evaluation of unscheduled DNA synthesis (UDS). All six cooked food mutagens examined produced concentration-dependent inc reases 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 ran k order of potency was not apparent in either rat or mouse liver slice s. In rat liver slices only MeIQ significantly induced UDS, although p ositive results were obtained with two other genotoxins, namely 2-acet ylaminofluorene and aflatoxin B-1. Apart from MeIQ(x), all the cooked fi,od mutagens produced significant increases in UDS in mouse liver sl ices. This study demonstrates the usefulness of precision-cut liver sl ices to evaluate species differences in xenobiotic-induced genotoxicit y. Both marked compound and species differences in induction of UDS we re observed. The data provide further evidence that dietary cooked foo d mutagens are potential human carcinogens. (C) Crown Copyright 1998 P ublished by Elsevier Science Ltd. All lights reserved.