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 Amol/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 adenosine triphosphatase. Immunohistochemical staining of consecutive sections using an anti-STa rabbit antibody demonstrated that STa was expressed at decreased levels in most of the adenosine triphosphatase-negative liver foci. This effect was observed in both 1-hydroxymethylpyrene- and phenobarbital-treated animals. The decrease in STa content in enzyme-altered foci may lead to a selective advantage of the preneoplastic cells in the presence of agents that are able to form reactive sulfuric acid esters, such as 1-hydroxymethylpyrene. In some diethyl-nitrosamine/phenobarbital-treated rats, a small number of atypical foci were observed, most of them showing enhanced expression of STa and unchanged to moderately increased ATPase activity.