0000000000546681
AUTHOR
Gisela Werle-schneider
External Versus Internal Metabolic Activation of Polycyclic Aromatic Compounds in Mutagenicity Tests: A Comparison Using Heterologous Expression Systems
Abstract Benzo[a]pyrene-trans-7,8-dihydrodiol was virtually non-mutagenic to Chinese hamster V79p cells, but was strongly mutagenic to a V79-derived cell line expressing cytochrome P450 1A1, when the cells were exposed separately. In mixed cultures of these two cell types, it showed about 50 % of the mutagenic activity in V79p cells, compared to that observed in the enzyme-proficient cell line, indicating an efficient intercellular transfer of the active metabolite. The benzylic alcohols 1-hydroxymethylpyrene and 6-hydroxymethylbenzo[a]-pyrene were weakly mutagenic to Salmonella typhimurium TA1538 in the absence of a metabolic activation system, but were potent mutagens to a TA1538-derived …
Development of hydroxysteroid sulfotransferase-deficient lesions during hepatocarcinogenesis in rats
Rat liver cytosolic hydroxysteroid sulfotransferases form highly reactive sulfuric acid esters from some benzylic alcohols, such as 1-hydroxymethylpyrene. In this study we examined the expression of hydroxysteroid sulfotransferase a (STa) in carcinogen-induced enzyme-altered, presumably preneoplastic, rat liver foci. Female Wistar rats were given a single i.p. injection of diethylnitrosamine (0.15 mumol/g body wt) 1 day after birth to induce the liver foci. After weaning, rats were given 1-hydroxymethylpyrene or phenobarbital continuously in their diet (250 or 500 p.p.m. respectively) for a total of 120 days. Carcinogen-induced liver foci were identified by a change in the marker enzyme ade…