Sulphotransferase-mediated activation of the carcinogen 5-hydroxymethyl-chrysene. Species and sex differences in tissue distribution of the enzyme activity and a possible participation of hydroxysteroid sulphotransferases

Biochem Pharmacol. 1989 Sep 15;38(18):3003-9. doi: 10.1016/0006-2952(89)90008-7.

Abstract

Sulphation of the carcinogen 5-hydroxymethyl-chrysene (5-HCR) to the active metabolite 5-HCR sulphate occurred at significant rates in all of hepatic cytosols prepared from the male and female experimental animals, rats, mice, guinea-pigs and hamsters. The 5-HCR-sulphating activity was also found in kidney cytosols of all the experimental animals used, while their activities were much less than those of hepatic cytosols. In the male mice, the enzyme activity of testis was higher than any other examined tissue. Small intestine and adrenal of male and female guinea-pigs had relatively high enzyme activities. Small enzyme activities were also found in a variety of extrahepatic tissues of some of these animals. Marked species and sex differences (female much greater than male in the rat and mouse) were observed in the hepatic enzyme activity. In the female rat liver which showed the highest 5-HCR-sulphating activity among the examined tissues of all the animals, a typical hydroxysteroid sulphotransferase inhibitor, dehydroepiandrosterone (DHA) sulphate (1 mM), potently and competitively inhibited the sulphation of 5-HCR as well as that of DHA, a typical substrate for hydroxysteroid sulphotransferases. On the contrary, the phenol sulphotransferase inhibitors, pentachlorophenol and 2,6-dichloro-4-nitrophenol, had only a little effect on these enzyme activities even at a concentration of 50 microM that showed a potent inhibition of the phenol sulphotransferase activity. These results suggest that 5-HCR be sulphated in the female rat liver by hydroxysteroid sulphotransferases, but not by phenol sulphotransferases.

MeSH terms

  • Animals
  • Biotransformation
  • Carcinogens / metabolism*
  • Chrysenes / metabolism*
  • Cricetinae
  • Female
  • Guinea Pigs
  • Male
  • Mesocricetus
  • Mice
  • Phenanthrenes / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Sex Factors
  • Species Specificity
  • Sulfotransferases / analysis*
  • Sulfurtransferases / metabolism*

Substances

  • Carcinogens
  • Chrysenes
  • Phenanthrenes
  • 5-hydroxymethylchrysene
  • Sulfurtransferases
  • Sulfotransferases
  • alcohol sulfotransferase