Journal Article

Strain dependent effects of sex hormones on hepatocarcinogenesis in mice

Therese M. Poole and Norman R. Drinkwater

in Carcinogenesis

Volume 17, issue 2, pages 191-196
Published in print February 1996 | ISSN: 0143-3334
Published online February 1996 | e-ISSN: 1460-2180 | DOI:
Strain dependent effects of sex hormones on hepatocarcinogenesis in

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In order to study the interaction of genetic and hormonal factors during murine hepatocarcinogenesis, we compared the number of liver tumors induced by treatment of 12-day-old mice with N-N-diethyInitrosamine (DEN) (0.05μmol/ body wt) in intact mice and animals gonadectomized at 8 weeks of age from the three inbred strains, C3H/HeJ (C3H), C57BL/6J (B6), and C57BR/cdJ (BR). At 50 weeks of age, the mean liver tumormultiplicity in intact BR females was 28 ± 13, while that for intact female C3H and B6 mice was 1.4 ±4.7 and0.5 ± 1.0, respectively. In ovariectomized mice, the yield of liver tumors was ∼8-fold higher than in intactC3H (10.3 ± 7.5) and B6(4.1 ± 6.6) females. Only a slight increase (35 ± 14) was seen in ovariectomized BR females compared to intact BR females. Castration resulted in lower mean tumor multiplicities at 32 weeks of age in the males of all three strains. Intact male C3H, B6, and BR mice had mean liver tumor multiplicities of 61 ± 34, 7.4 ± 13, and 26± 18, respectively, while the mean tumor multiplicities in cas-trated C3H, B6, and BR mice were 24 ± 14, 0.5 ± 0.9, and 6.1± 10 tumors per mouse, respectively. The apparent rate of growth of glucose-6-phosphatase-deficient, preneoplastic foci in DEN-treated BR females was significantly higher than in B6 females. Thegrowth rates of hepatic foci in BR and B6 males were similar but foci in BR males were 5-fold more numerous than in B6 males. The high sensitivity of BR females may be due, at least in part, to the failure of ovarian hormones to inhibit the growth of preneoplastic foci and the subsequent development of liver tumors. Since BR males had a larger number of hepatic foci, it is likely that androgens increase the rate of focus formation in BR males.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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