Heston W E
J Toxicol Environ Health Suppl. 1976;1:257-66.
In testing for any carcinogenic effect of certain hormones the choice of test strain or strains is extremely important. By selecting several inbred strains one obtains maximum genetic variability offering a greater chance of demonstrating carcinogenesis in regard to a number of organs or tissues. The five strains of mice chosen in this study (C3H/He, C3HfB/He, BALB/cHe, A/He, and C5BL/He) provided a test for effect of Enovid at sterilizing doses on occurrence of mammary tumors, ovarian tumors, hepatomas, cervical and vaginal tumors, adrenocortical adenomas, and hypophyseal tumors. Results indicated a slight inhibitor effect of Enovid on mammary tumors in C3H and adrenocortical adenomas in BALB/c and an even greater inhibiotry effect on hepatomas in C3HfB. No effect on ovarian tumors could be detected in the appropriate test provided by C3HfB. In BALB/c females epithelial lesions of the cervix and vagina were observed in both the treated females and the controls with a slight increase in the group treated with the highest dose. All were small lesions observed only in the histologic section. None had invaded beyond the wall of the vagina, and none had metastasized. None could be classified as a frank carcinoma. In the group treated with the highest dose of Enovid, the lesions showed slightly further progression than in the other groups. The most significant tumorigenic effect of the Enovid was the increase in hypophyseal tumors in the C5BL females at advanced age. Direct extrapolation from one strain to another, from one species to another, from mouse to humans, or from one human being to another would be risky because of genetic differences. Approaches to the problem in human beings are, however, suggested. Because of these observations in mice, it would be well, if possible, to collect hypophyses of women at postmortem who have previously been on birth control pills for some time and send these hypophyses to some central laboratory where they can be examined for any changes that might be attributed to the use of the antifertility drug.
在检测某些激素的致癌作用时，选择一种或几种试验菌株极为重要。通过选择几种近交系，可获得最大的遗传变异性，从而更有可能在多个器官或组织中证明致癌作用。本研究选用的五株小鼠（C3H/He、C3HfB/He、BALB/cHe、A/He和C5BL/He）用于测试炔雌醇甲醚绝育剂量对乳腺肿瘤、卵巢肿瘤、肝癌、宫颈和阴道肿瘤、肾上腺皮质腺瘤以及垂体肿瘤发生的影响。结果表明，炔雌醇甲醚对C3H小鼠的乳腺肿瘤以及BALB/c小鼠的肾上腺皮质腺瘤有轻微抑制作用，对C3HfB小鼠的肝癌抑制作用更强。在C3HfB提供的相应试验中，未检测到对卵巢肿瘤有影响。在BALB/c雌性小鼠中，治疗组和对照组均观察到宫颈和阴道上皮病变，最高剂量治疗组病变略有增加。所有病变均为小病变，仅在组织学切片中观察到。无一例侵犯超过阴道壁，无一例发生转移。无一例可归类为明显的癌。在接受最高剂量炔雌醇甲醚治疗的组中，病变进展略快于其他组。炔雌醇甲醚最显著的致瘤作用是老年C5BL雌性小鼠垂体肿瘤增加。由于存在遗传差异，从一个菌株直接推断到另一个菌株、从一个物种直接推断到另一个物种、从小鼠直接推断到人类或从一个人直接推断到另一个人都存在风险。然而，文中提出了针对人类问题的研究方法。鉴于在小鼠中的这些观察结果，如果可能的话，最好收集曾服用避孕药一段时间的女性死后的垂体，将这些垂体送到某个中央实验室，在那里检查是否有任何可能归因于使用抗生育药物的变化。
