Purdy R H, Marshall M V
Carcinogenesis. 1984 Dec;5(12):1709-15. doi: 10.1093/carcin/5.12.1709.
Ethinyl estradiol, the estrogenic component of oral contraceptives, has been shown to enhance the mutagenicity of 2-aminofluorene, 2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, and N-acetoxy-2-acetylaminofluorene with strain TA 98 of Salmonella typhimurium and various rat liver activating systems. The magnitude of the enhancement of mutation produced by ethinyl estradiol is dependent upon: the type of mixed-function oxidase inducer of the liver activating system; the structure and concentration of the arylamine; the concentration of ethinyl estradiol; and metabolism of ethinyl estradiol to its catechol, 2-hydroxyethinyl estradiol, by the activating system. Moxestrol, a biologically potent estrogenic derivative of ethinyl estradiol which is not metabolized effectively to its catechol by the mixed-function oxidases, does not enhance the mutagenicity of the above arylamines and related compounds. Both 2-hydroxyethinyl estradiol and 2-hydroxymoxestrol enhance the mutagenicity of 2-aminofluorene and 2-acetylaminofluorene. Neither the estrogens nor their catechols are mutagenic by themselves in this system. In the presence of ethinyl estradiol, a marked inhibition of ring hydroxylation of 2-acetylaminofluorene was demonstrated. Since ring hydroxylation is a well established detoxification pathway of arylamine and arylamide metabolism, the enhancement of mutagenicity by ethinyl estradiol may be the result of a net increase in N-hydroxylation of arylamines and arylamides.
炔雌醇是口服避孕药中的雌激素成分，已证明它能增强2-氨基芴、2-乙酰氨基芴、N-羟基-2-乙酰氨基芴和N-乙酰氧基-2-乙酰氨基芴在鼠伤寒沙门氏菌TA 98菌株及各种大鼠肝脏活化系统中的诱变性。炔雌醇所产生的突变增强程度取决于：肝脏活化系统中混合功能氧化酶诱导剂的类型；芳胺的结构和浓度；炔雌醇的浓度；以及活化系统将炔雌醇代谢为其儿茶酚即2-羟基炔雌醇的情况。莫昔司琼是炔雌醇的一种具有生物活性的雌激素衍生物，它不能被混合功能氧化酶有效地代谢为其儿茶酚，不会增强上述芳胺及相关化合物的诱变性。2-羟基炔雌醇和2-羟基莫昔司琼均可增强2-氨基芴和2-乙酰氨基芴的诱变性。在该系统中，雌激素及其儿茶酚本身均无诱变性。在炔雌醇存在的情况下，已证明2-乙酰氨基芴的环羟基化受到明显抑制。由于环羟基化是芳胺和芳酰胺代谢中一个公认的解毒途径，炔雌醇对诱变性的增强作用可能是芳胺和芳酰胺N-羟基化净增加的结果。
