Initiation and Promotion of Enzyme-Altered Foci in Rat Liver by 1-Hydroxymethylpyrene

Abstract

1-Hydroxymethylpyrene (HMP) was tested for the initiation and promotion of ATPase-negative foci in rat liver. It showed weak initiating activity and pronounced promoting activity. However, the promoting activity was only observed in females. This sex difference correlates with the sex-dependent expression of hydroxysteroid sulfotransferase a (STa), an enzyme capable of activating HMP to a cytotoxic sulfuric acid ester. Since STa was repressed in the ATPase-negative foci, selective toxification and toxicity in the normal parenchyma of female rats may be a mechanism of the observed promotion.

Key Words:

• Benzylic alcohols
• enzyme-altered foci
• hepatocarcinogenesis
• 1-hydroxymethylpyrene
• reactive metabolites
• sulfotransferase.