Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors

To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (DEN) on the induction of histochemically detectable altered hepatocyte foci and hepatic tumors, we assessed the yields of these lesions in the livers of 150-day-old rats that had been treated neonatally with a single dose of gamma radiation and i.p.-injected DEN, either separately or in combination. The focus population was examined for two histochemical markers (elevated gamma glutamyl transpeptidase [GGT(+)] and iron exclusion [FE(-)] ), giving rise to three detectable focus phenotypes, i.e. GGT(+) foci, FE(-) foci, and GGT(+), FE(-) foci. These results suggest that (i) phenotypically distinguishable lesions, including foci with different histochemical marker patterns and tumors, originate from specific types of damage at different genetic loci and are developmentally independent; and (ii) the expression of the GGT(+) market per se in altered hepatocyte foci is not a reliable index of incipient hepatic neoplasia. (author)