Sex-dependent expression of class pi glutathione S-transferase during chemical hepatocarcinogenesis in B6C3F1 mice.

Expression of class pi glutathione S-transferase (GST-II) was investigated during chemical hepatocarcinogenesis in female and male mice. Diethylnitrosamine (DEN; 10 mg/kg body wt) was administered to B6C3F1 mice on day 15 after birth, and liver sections were immunohistochemically stained with GST-II antibody at 12 and 24 weeks thereafter. In the normal mouse liver, GST-II was strongly expressed in males but only weakly in females. At 24 weeks after DEN treatment, the majority of preneoplastic foci could be detected as GST-II-positive in the female mice, while those in males were observed as to have decreased GST-II relative to the background. Class alpha GST-I and class mu GST-III did not exhibit any remarkable changes in preneoplastic foci. This result indicates that GST-II is a useful positive and negative marker for preneoplastic lesions in female and male mouse livers. In addition, class pi GST-II may be useful for the rapid screening hepatocarcinogens in mice because GST-II-positive or -negative single cells and minifoci, considered as precursor initiated populations, were detectable in females and males at 12 weeks after the DEN injection.