ADDITIVE ACTION OF FIVE HETEROCYCLIC AMINES IN TERMS OF INDUCTION OF GTS-P POSITIVE SINGLE CELLS AND FOCI IN RAT LIVER-CORRELATION WITH DNA ADDUCT FORMATION

Abstract

The relation between induction of both single GST-P positive hepatocytes and foci was assessed after treatment with 0.015% Trp-P-1, 0.05% Glu-P-2, 0.03% IQ, 0.03% MeIQ, 0.04% McIQx alone or in combinations of all five at 1/5 or 1/25 of these individual dietary doses for 6 weeks, partial hepatectomy being performed at week 1. A good correlation between induction of single cells and focal lesions was observed. Additional analysis of covalent binding of heterocyclic amines to rat liver DNA by the 32P-postlabeling method revealed a good fit with yield of preneoplastic lesions. The results thus suggest that DNA adducts resulting from exposure to heterocyclic amines play an important role in the earliest stages of chemical carcinogenesis in the rat liver.