Nakamura Y, Kodama M, Kodama T
Gan. 1981 Oct;72(5):679-83.
The excretion of urinary steroids were investigated in rats in the course of mammary carcinogenesis by 7, 12-dimethylbenz [a] anthracene (DMBA). The carcinogen was fed to female Sprague-Dawley rats on days 50 and 64 after birth at a dose of 10 mg each. The excretion of urinary androgen, 11-deoxy-17-oxosteroid (11-DOOS), increased temporarily (at 80 days of age) in DMBA-treated rats as compared with non-treated controls. The excretion of adrenal corticosteroid, 17-deoxy-corticosteroid (17-DOCS), was lower than normal in the rats that failed to develop tumors within 200 days after receiving DMBA. The difference between the above non-responders and the tumor-developing responders (or the non-treated controls) was significant at 80 and 120 days of age, but not at 160 days of age. The final tumor weights at 160 days of age were also positively correlated to the excretion of 17-DOCS at 130 days of age. It was indicated that the overall process of DMBA carcinogenesis could be promoted by the endogenous adrenocortical steroids. The possible mechanism underlying the production of mammary cancer is discussed in the light of the metabolic intimacy between DMBA and the adrenal steroids.
通过7,12-二甲基苯并[a]蒽(DMBA)诱导大鼠发生乳腺癌的过程中,对大鼠尿甾体排泄情况进行了研究。致癌剂在出生后第50天和第64天以每只10毫克的剂量喂给雌性斯普拉格-道利大鼠。与未处理的对照组相比,经DMBA处理的大鼠尿雄激素、11-脱氧-17-氧代甾体(11-DOOS)的排泄量在80日龄时暂时增加。在接受DMBA后200天内未发生肿瘤的大鼠中,肾上腺皮质类固醇、17-脱氧皮质类固醇(17-DOCS)的排泄量低于正常水平。上述无反应者与发生肿瘤的反应者(或未处理的对照组)之间的差异在80日龄和120日龄时显著,但在160日龄时不显著。160日龄时的最终肿瘤重量也与130日龄时17-DOCS的排泄量呈正相关。结果表明,内源性肾上腺皮质类固醇可促进DMBA致癌的整个过程。根据DMBA与肾上腺类固醇之间的代谢密切关系,讨论了乳腺癌发生的可能机制。