ROLE OF MUTAGENESIS IN CARCINOGENESIS

大多数化学致癌物会导致DNA损伤，并在特定情况下具有致突变性 然而，某些致癌物(包括人类 致癌物质己烯雌酚(DES)、石棉、砷化合物、苯和 睾丸激素)通常不会导致基因突变。我们检查了 这些化学物质诱导形态转化的能力，基因 叙利亚仓鼠胚胎(SHE)细胞的突变和染色体突变 在文化上。因为含有雄激素和雌激素的化合物 与动物和人类的致癌有关，我们探索了 自然发生选择和综合选择的机理研究 产生荷尔蒙。先前的研究表明，天然雌激素 (17-雌二醇)和合成雌激素(DES)具有细胞功能 SHE细胞在培养中的转化。诱变变化的作用 (非整倍体诱导和DNA损伤) 对化合物进行了研究。睾酮，丙酸睾丸酮，17- 曲安奈德和黄体酮，代表主要的内源性和 人工合成的雄激素和孕激素被评估为可能的细胞 SHE细胞的转化和遗传效应。睾丸激素和睾丸- 丙酸特龙的毒性比其他两种类固醇低。 特龙、丙酸睾丸酮和孕酮诱导的形态 转化频率相近的SHE细胞的转化。多数 丙酸睾丸酮有很强的疗效。17-曲安奈德 在测试的任何剂量下都没有诱导细胞转化。转化 睾酮、丙酸睾丸酮和前列腺素诱导的频率- Erone还不到苯并[a]吡喃诱导的一半。 这些类固醇导致染色体频率显著增加。 是口粮还是非整倍体。没有观察到基因突变 睾丸激素这些类固醇也与致癌有关 体内活性，这些体外发现提供了一个模型和新的见解 雄激素和孕激素诱导细胞机制的研究进展 转型。

Most chemical carcinogens induce DNA damage and are mutagenic at specific genetic loci; however, certain carcinogens (including the human carcinogens diethylstilbestrol (DES), asbestos, arsenicals, benzene and testosterone) usually do not induce gene mutations. We examined the ability of these chemicals to induce morphological transformation,gene mutations and chromo- some mutations in Syrian hamster embryo (SHE) cells in culture. Because androgenic and estrogenic compounds have been associated with cancer induction in animals and humans, we explored mechanistic studies of select naturally occurring and synthetically produced hormones. Previous studies showed that natural estrogens (17deltax-estradiol) and synthetic estrogen (DES) are capable of cell transformation of SHE cells in culture. The role of mutagenic changes (aneuploidy induction and DNA damage) in transformation by estrogenic compounds was studied. Testosterone, testosterone propionate, 17- trenbolone and progesterone, which represent the main endogenous and synthetic androgens, and a progestin, were evaluated for possible cell transformation and genetic effects in SHE cells. Testosterone and testos- terone propionate were less toxic than the other two steroids.Testos- terone, testosterone propionate and progesterone induced morphological transformation of SHE cells with similar transformation frequencies. Most potent effects were observed with testosterone propionate. 17-Trenbolone did not induce cell transformations at any dose tested. Transformation frequencies induced by testosterone, testosterone propionate and progest- erone were less than one-half that induced by benzo[a]pyrene.None of these steroids induced significant increases in frequencies of chromosome aber- rations or aneuploidy. Gene mutations were not observed for testosterone These steroids are also associated with carcinogenic activity in vivo,these in vitro findings provide a model and new insights into the study of the mechanisms of androgen- and progestin- induced cell transformation.