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螯合剂非整倍体诱导特性的进一步证据:乙二胺四乙酸对小鼠雄性生殖细胞微核的诱导作用

Further evidence for the aneuploidogenic properties of chelating agents: induction of micronuclei in mouse male germ cells by EDTA.

作者信息

Russo A, Levis A G

机构信息

Department of Biology, University of Padova, Italy.

出版信息

Environ Mol Mutagen. 1992;19(2):125-31. doi: 10.1002/em.2850190206.

DOI:10.1002/em.2850190206
PMID:1541253
Abstract

A micronucleus assay based on cytogenetic analysis of early spermatids (Tates et al.; Mutation Research 121:131-138, 1983) was applied to determine if the chelating agent ethylenedinitrilotetraacetic acid (EDTA) may induce aneuploidy in mouse meiotic cells. Previous results indicated aneuploidogenic activity of EDTA in Drosophila female germ cells (induction of chromosome loss; Zordan et al.: Environ Mol Mutagen 15:205-213, 1990). In the same study, a standard aneuploidy test based on chromosome counting in mouse secondary spermatocytes failed however to show aneuploidogenic properties of EDTA in mouse somatic and germ cells. In the present study the effects of two clastogens, adriamycin (ADM) and mitomycin C (MMC), and of the aneuploidogenic agent chloral hydrate (CH) were also evaluated. All compounds were tested at a single dose level and at two time intervals corresponding to the treatment of diakinesis/metaphase I/metaphase II spermatocytes. The clastogenic potential of the compounds under study was also evaluated, by chromosomal aberration analysis in mouse spermatogonia, in an independent set of experiments. The results obtained indicate that ADM, CH and EDTA are able to induce micronuclei at meiosis. On the contrary, only ADM and MMC induced chromosomal aberrations in mouse spermatogonia. Therefore, the most probable origin of micronuclei produced by CH and EDTA is whole chromosome lagging. These results provide further evidence for the aneuploidogenic properties of these chelating agents.

摘要

基于早期精细胞细胞遗传学分析的微核试验(泰茨等人;《突变研究》121:131 - 138,1983年)被用于确定螯合剂乙二胺四乙酸(EDTA)是否会在小鼠减数分裂细胞中诱导非整倍体。先前的结果表明EDTA在果蝇雌性生殖细胞中具有非整倍体诱导活性(诱导染色体丢失;佐丹等人:《环境与分子突变》15:205 - 213,1990年)。然而,在同一项研究中,基于小鼠次级精母细胞染色体计数的标准非整倍体试验未能显示EDTA在小鼠体细胞和生殖细胞中的非整倍体诱导特性。在本研究中,还评估了两种致断裂剂阿霉素(ADM)和丝裂霉素C(MMC)以及非整倍体诱导剂水合氯醛(CH)的作用。所有化合物均在单一剂量水平以及与双线期/中期I/中期II精母细胞处理相对应的两个时间间隔进行测试。在一组独立实验中,还通过小鼠精原细胞的染色体畸变分析评估了所研究化合物的致断裂潜力。获得的结果表明,ADM、CH和EDTA能够在减数分裂时诱导微核。相反,只有ADM和MMC在小鼠精原细胞中诱导了染色体畸变。因此,CH和EDTA产生的微核最可能的来源是整条染色体滞后。这些结果为这些螯合剂的非整倍体诱导特性提供了进一步的证据。

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