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Induction of complete and mosaic sex-linked recessive lethal mutations by cigarette smoke filtrate in Drosophila melanogaster

机译:果蝇的香烟烟雾滤液诱导完全和镶嵌性相关的隐性致死性突变

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The genotoxic effects of cigarette smoke filtrate (SF) on the germ-line stages were examined in Drosophila melanogaster using the sex-linked recessive lethal test, which detects a broad spectrum of genetic alterations and proved to show correlations between mutagenicity and carcinogenicity of the tested chemicals. SF was extracted from fiberglass filter cartridges; each used in smoking 15 cigarettes. The proper SF concentrations (0.2 mu L) in 0.45% NaCl saline were injected intraperitoneally in 2- to 3-day-old wild-type males, alongside with controls injected with 0.2 mL of saline. The genotoxicity effects of SF were examined in all spermatogenesis stages of treated males. Results showed that SF was toxic with an median lethal dose value of approximately 0.2% and induced significant sterility effects. The mutagenicity of SF (0.2%) was significantly stage specific and induced complete sex-linked recessive lethal mutations in the broods representing the spermatocytes and late and early spermatogonia, and induced mosaic mutations in the untreated progeny in the brood representing late spermatogonia. These results indicated, for the first time, that SF induces mosaic mutations, which could result from DNA instabilities and labile permutations that can be replicated and passed to future generations before being fixed into mutations in the untreated progeny of treated males, or originating from mutations that result in increasing hyperplasia of the gonad that subsequently produce the actual mutations in later cell cycles. Such delayed mutagenic effects of SF indicated that SF and, consequently, cigarette smoking have much greater genotoxicity than what was previously predicted.
机译:使用性连锁隐性致死试验在果蝇中检测了香烟烟雾滤液(SF)对种系阶段的遗传毒性作用,该试验可检测到广泛的遗传改变,并证明显示出致突变性和致癌性之间的相关性化学药品。 SF是从玻璃纤维滤筒中提取的;每支抽15支香烟。在2至3天大的野生型雄性小鼠中,腹膜内注射0.45%NaCl生理盐水中适当的SF浓度(0.2μL),并注入0.2 mL生理盐水。在所治疗的男性的所有精子形成阶段都检查了SF的遗传毒性作用。结果表明,SF具有毒性,中位致死剂量值为约0.2%,并具有明显的无菌作用。 SF(0.2%)的致突变性具有明显的阶段特异性,并在代表精子细胞以及晚期和早期精原细胞的育雏中诱导了完全的性连锁隐性致死突变,并在代表晚期精原细胞的育雏的未处理后代中诱导了镶嵌突变。这些结果首次表明,SF诱导了镶嵌突变,这可能是由于DNA不稳定性和不稳定的排列所致,这些变异可以被复制并传给后代,然后再固定在未经处理的雄性子代的突变中,或源自突变。导致性腺增生增加,随后在以后的细胞周期中产生实际的突变。 SF的这种延迟诱变作用表明,SF和因此吸烟的遗传毒性比以前预测的要大得多。

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