ROLE OF MUTAGENESIS IN CARCINOGENESIS

诱变在致癌过程中的作用

• 批准号: 6162167
• 负责人: JAMES C. BARRETT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162167
• 关键词: DNA damage; carcinogen testing; chemical carcinogen; chemical carcinogenesis; diethylstilbestrol; embryo /fetus tissue /cell culture; estradiol; estrogen inhibitor; estrogens; hamsters; mutagen testing; mutagens; tamoxifen

Summary of Work: 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 chromosome mutations in Syrian hamster embryo (SHE) cells in culture. To examine the ability of estrogens and anti-estrogens to induce cellular transformation and genetic effects, Syrian hamster embryo (SHE) cells were treated with estrogens, 17beta-estradiol (E2) or diethystilbestrol (DES), or with anti-estrogens, tamoxifen (TAM), toremifene (TOR) or ICI 164,384. Treatment with each chemical at 1-30uM for 48 hrs caused morphological transformation of SHE cells in a dose related fashion. The highest frequency was exhibited in SHE cells treated with DES. TOR showed a higher transforming ability when compared to the other anti-estrogens (TAM and ICI 164,348). No significant increases in the frequencies of chromosomal aberrations were observed in SHE cells that were treated with any of the chemicals. However, treatment of SHE cells with each chemical induced a dose-dependent increase of aneuploid cells in the near diploid range. Our results indicate that the ability of the estrogens and anti- estrogens to induce numerical chromosomal abnormality may be involved in their cell transformation activity and potential carcinogenicity. Benzene is a human carcinogen present naturally in petroleum and gasoline. For the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity, benzene and it's principal metabolites, phenol, catechol, and hydroquinone were examined for their ability to induce cell transformation of genotoxic effects using the same mammalian cells in culture. Each of the four compounds induced morphological transformation of Syrian hamster embryo (SHE) cells.

工作总结：大多数化学致癌物会导致DNA损伤，并 在特定的遗传位点上具有突变性；然而，某些致癌物质 (包括人类致癌物质己烯雌酚(DES)、石棉、 砷、苯和睾酮)通常不会诱导基因 突变。我们检查了这些化学物质诱导 小鼠的形态转化、基因突变和染色体突变 叙利亚仓鼠胚胎(SHE)细胞在培养中。考查…的能力 雌激素和抗雌激素诱导细胞转化和 遗传效应，叙利亚仓鼠胚胎(SHE)细胞用 雌激素，17β-雌二醇(E_2)或己烯雌酚(DES)，或与 抗雌激素，他莫昔芬()，托瑞米芬(TOR)或ICI164,384。 每种化学物质在1-30uM下处理48小时，引起形态 SHE细胞以剂量相关方式转化。最高的 在用DES处理的SHE细胞中出现频率。托尔展示了一个 与其他抗雌激素相比，转化能力更强 (和ICI164,348)。没有显著增加的频率 在SHE细胞中观察到染色体的异常。 任何一种化学物质。然而，每种化学物质对SHE细胞的处理 诱导近二倍体细胞非整倍体细胞的剂量依赖性增加 射程。我们的结果表明，雌激素和抗卵巢癌的能力 雌激素诱导染色体数目异常可能参与 它们的细胞转化活性和潜在的致癌性。 苯是一种人类致癌物，天然存在于石油和 汽油。用于同时评估苯诱导的 致癌和致突变，苯及其主要代谢物， 苯酚、邻苯二酚和对苯二酚的能力被检测。 用相同的哺乳动物诱导遗传毒性效应的细胞转化 培养中的细胞。四种化合物中的每一种均可诱导形态 叙利亚仓鼠胚胎(SHE)细胞的转化。