Influence of dehydroepiandrosterone, diaminopropane and butylated hydroxyanisole treatment during the induction phase of rat liver nodular lesions in a short-term system.

The effects of concomitant treatment with dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), diaminopropane (DAP), an inhibitor of ornithine decarboxylase or the microsomal drug detoxifying enzyme inducer butylated hydroxyanisole (BHA) during the induction phase of rat liver nodular lesion development were investigated. Clear reductions in both number and size of foci and nodules as assayed quantitatively with the aid of marker enzymes G6PD, glutathione S-transferase P form or gamma-glutamyl transpeptidase were established for treatment with either DHEA or BHA. DAP in contrast did not exert influence on the number of lesions, but brought about a significant reduction in size. The quantitative data taken together with the finding that increased labelling of tritiated thymidine occurred in extrafocal hepatocyte populations in BHA-treated animals, give direct support to the view that alteration in enzyme phenotype within putative pre-neoplastic lesions plays a central role in their generation with this short-term model. In particular, a physiological adaptive significance of G6PD elevation is suggested.