Poole T M, Drinkwater N R
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
Carcinogenesis. 1996 Feb;17(2):191-6. doi: 10.1093/carcin/17.2.191.
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-diethylnitrosamine (DEN) (0.05 mumol/g 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 tumor multiplicity in intact BR females was 28 +/- 13, while that for intact female C3H and B6 mice was 1.4 +/- 4.7 and 0.5 +/- 1.0, respectively. In ovariectomized mice, the yield of liver tumors was approximately 8-fold higher than in intact C3H (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 castrated 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. The growth 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.
为了研究小鼠肝癌发生过程中遗传和激素因素的相互作用，我们比较了用N,N-二乙基亚硝胺（DEN）（0.05 μmol/g体重）处理12日龄的完整小鼠以及8周龄时进行性腺切除的来自三个近交系（C3H/HeJ（C3H）、C57BL/6J（B6）和C57BR/cdJ（BR））的小鼠所诱导的肝肿瘤数量。在50周龄时，完整的BR雌性小鼠的平均肝肿瘤多发性为28±13，而完整的C3H和B6雌性小鼠分别为1.4±4.7和0.5±1.0。在去卵巢小鼠中，肝肿瘤的发生率比完整的C3H（10.3±7.5）和B6（4.1±6.6）雌性小鼠高约8倍。与完整的BR雌性小鼠相比，去卵巢的BR雌性小鼠仅略有增加（35±14）。阉割导致所有三个品系的雄性小鼠在32周龄时平均肿瘤多发性降低。完整的雄性C3H、B6和BR小鼠的平均肝肿瘤多发性分别为61±34、7.4±13和26±18，而去势的C3H、B6和BR小鼠的平均肿瘤多发性分别为每只小鼠24±14、0.5±0.9和6.1±10个肿瘤。在DEN处理的BR雌性小鼠中，葡萄糖-6-磷酸酶缺乏的癌前病灶的表观生长速率显著高于B6雌性小鼠。BR和B6雄性小鼠肝病灶的生长速率相似，但BR雄性小鼠的病灶数量是B6雄性小鼠的5倍。BR雌性小鼠的高敏感性可能至少部分归因于卵巢激素未能抑制癌前病灶的生长以及随后肝肿瘤的发生。由于BR雄性小鼠有更多的肝病灶，雄激素很可能增加了BR雄性小鼠中病灶形成的速率。
