DEVELOPMENT OF HYDROXYSTEROID SULFOTRANSFERASE-DEFICIENT LESIONS DURING HEPATOCARCINOGENESIS IN RATS

Rat liver cytosolic hydroxysteroid sulfotransferases form highly react ive sulfuric acid esters from some benzylic alcohols, such as 1-hydrox ymethylpyrene. In this study we examined the expression of hydroxyster oid sulfotransferase a (STa) in carcinogen-induced enzyme-altered, pre sumably preneoplastic, rat liver foci. Female Wistar rats were given a single i.p. injection of diethylnitrosamine (0.15 Amol/g body wt) 1 d ay after birth to induce the liver foci. After weaning, rats were give n 1-hydroxymethylpyrene or phenobarbital continuously in their diet (2 50 or 500 p.p.m. respectively) for a total of 120 days. Carcinogen-ind uced liver foci were identified by a change in the marker enzyme adeno sine triphosphatase. Immunohistochemical staining of consecutive secti ons using an anti-STa rabbit antibody demonstrated that STa was expres sed at decreased levels in most of the adenosine triphosphatase-negati ve liver foci. This effect was observed in both 1-hydroxymethylpyrene- and phenobarbital-treated animals. The decrease in STa content in enz yme-altered foci may lead to a selective advantage of the preneoplasti c cells in the presence of agents that are able to form reactive sulfu ric acid esters, such as 1-hydroxymethylpyrene. In some diethyl-nitros amine/phenobarbital-treated rats, a small number of atypical foci were observed, most of them showing enhanced expression of STa and unchang ed to moderately increased ATPase activity.