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Sex Differences in Cell Proliferation and N-Hydroxy-2-acetylaminofluorene Sulfotransferase Levels in Rat Liver during 2-Acetylaminofluorene Administration¹

Veterans Administration Hospital, and Department of Biochemistry, University of Tennessee, Memphis, Tennessee 38104

This study was initiated in an effort to determine the mechanism responsible for the different susceptibilities of male and female rats to the induction of liver tumors by 2-acetylaminofluorene (AAF). Gain in body weight of male and female rats maintained on a diet containing 0.04% AAF for 8 weeks was inhibited 38 and 32%, respectively, when compared with animals on a control diet. Liver weights (g liver per 100 g body weight) of females remained the same during the 8-week period, while those of males decreased slightly between Weeks 3 and 8.

During the first 4 weeks of AAF administration, livers of male rats had 5 to 10 times the levels of N-hydroxy-AAF sulfotransferase activity as had livers of females. The absolute amount of sulfotransferase activity in livers of both male and female rats declined markedly and was approximately 10 to 30% of control values at the end of 2 weeks. In spite of the marked decrease in sulfotransferase activity, activity of the enzyme in livers of male rats remained 2 to 3 times that of females throughout the 8-week period.

The mitotic index and incorporation of tritiated thymidine in livers of female rats were low and constant throughout the 8-week period. In contrast, both thymidine incorporation and mitotic index in livers of male rats exhibited a marked increase after 3 weeks. Little or no change in content of liver RNA or DNA was observed in either male or female rats during the 8-week period.

¹ Supported by the United States Veterans Administration and by USPHS Research Grant CA-05490 from the National Cancer Institute.

Received 1/31/72. Accepted 4/14/72.