Ja. Beamand et al., EFFECT OF SOME COOKED FOOD MUTAGENS ON UNSCHEDULED DNA-SYNTHESIS IN CULTURED PRECISION-CUT RAT, MOUSE AND HUMAN LIVER SLICES, Food and chemical toxicology, 36(6), 1998, pp. 455-466
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.