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7,12-二甲基苯并[a]蒽与仓鼠乳腺大分子的结合:服用炔雌醇或经胎盘暴露于己烯雌酚的影响。

The binding of 7,12-dimethylbenz[a]anthracene to mammary gland macromolecules in the hamster:effects of Enovid feeding or transplacental exposure to diethylstilboestrol.

作者信息

Hertzog P J, Lawson T A, Gingell R

出版信息

Chem Biol Interact. 1981 Oct;37(1-2):199-205. doi: 10.1016/0009-2797(81)90177-0.

Abstract

The covalent binding of 7,12-[3H]dimethylbenz[a]anthracene ([3H--DMBA) to mammary gland macromolecules was studied in hamsters fed a contraceptive mixture, Enovid, those exposed transplacentally to diethylstilboestrol (DES), and controls. Compared with rats, hamsters are relatively resistant to DMBA mammary carcinogenesis, but susceptibility is increased by either of the above treatments with Enovid or DES. The amount of DMBA bound to DNA and protein ws 4-5 times greater than to RNA, but only DNA binding was persistent. Fifty-three percent of the DNA-bound DMBA was still present after 8 days. The amount of DMBA bound to hamster mammary DNA and its persistence was similar to that found in rats. Neither Enovid nor DES treatment altered the levels of binding to mammary macromolecules, nor their persistence. These results indicate that the species differences in the susceptibility to DMBA-induced mammary carcinogenesis in hamsters and rats, and modification of the former by hormones, is not due to differences in the activation of carcinogens. The role of hormones such as prolactin in the promotion phase of mammary gland carcinogenesis may explain these differences.

摘要

研究了7,12-[3H]二甲基苯并[a]蒽([3H-DMBA])与喂食避孕药混合物炔雌醇甲醚(Enovid)的仓鼠、经胎盘暴露于己烯雌酚(DES)的仓鼠以及对照组仓鼠乳腺大分子的共价结合情况。与大鼠相比,仓鼠对DMBA诱导的乳腺癌发生相对具有抗性,但上述任何一种Enovid或DES处理都会增加其易感性。与RNA相比,与DNA和蛋白质结合的DMBA量要大4 - 5倍,但只有与DNA的结合是持久的。8天后,与DNA结合的DMBA仍有53%存在。与大鼠中发现的情况类似,与仓鼠乳腺DNA结合的DMBA量及其持久性与之相似。Enovid和DES处理均未改变与乳腺大分子的结合水平及其持久性。这些结果表明,仓鼠和大鼠对DMBA诱导的乳腺癌发生易感性的物种差异,以及激素对前者的改变,并非由于致癌物活化的差异。催乳素等激素在乳腺癌发生促进阶段的作用可能解释了这些差异。

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