Development of hydroxysteroid sulfotransferase-deficient lesions during hepatocarcinogenesis in rats

Carcinogenesis. 1993 Nov;14(11):2267-70. doi: 10.1093/carcin/14.11.2267.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / analysis
  • Animals
  • Biomarkers, Tumor / analysis
  • Carcinogens / toxicity*
  • Diethylnitrosamine / toxicity
  • Female
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / pathology
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / pathology*
  • Phenobarbital / toxicity
  • Pyrenes / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Sulfotransferases / deficiency
  • Sulfotransferases / metabolism*

Substances

  • Biomarkers, Tumor
  • Carcinogens
  • Pyrenes
  • Diethylnitrosamine
  • 1-hydroxymethylpyrene
  • Sulfotransferases
  • alcohol sulfotransferase
  • Adenosine Triphosphatases
  • Phenobarbital