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 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 diethylnitrosamine/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.
Werle-Schneider
G
G
Department of Toxicology, University of Mainz, Germany.
Schwarz
M
M
Glatt
H
H
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D010634:Phenobarbital / Q000633:toxicity; D011721:Pyrenes / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015238:Sulfotransferases / Q000172:deficiency / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002273:Carcinogens; D011721:Pyrenes; D004052:Diethylnitrosamine; C065833:1-hydroxymethylpyrene; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D000251:Adenosine Triphosphatases; D010634:Phenobarbital