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钒化合物在酵母和培养的哺乳动物细胞中的遗传毒性。

Genotoxicity of vanadium compounds in yeast and cultured mammalian cells.

作者信息

Galli A, Vellosi R, Fiorio R, Della Croce C, Del Carratore R, Morichetti E, Giromini L, Rosellini D, Bronzetti G

机构信息

Istituto di Mutagenesi e Differenziamento CNR, Pisa, Italy.

出版信息

Teratog Carcinog Mutagen. 1991;11(4):175-83. doi: 10.1002/tcm.1770110402.

DOI:10.1002/tcm.1770110402
PMID:1685805
Abstract

The ability of vanadium compounds to induce genetic activity was investigated in D7 and D61M strains of Saccharomyces cerevisiae and in Chinese hamster V79 cell line. In our previous work, ammonium metavanadate (pentavalent form, V5) induced mitotic gene conversion and point reverse mutation in the D7 strain of yeast. The genotoxicity was reduced by the presence of S9 fraction, which probably reduced pentavalent vanadium to the tetravalent form. In the present study, vanadyl sulfate (tetravalent form, V4) induced no convertants and revertants in yeast cells harvested from stationary growth phase. With yeast cells from logarithmic growth phase, which contain high levels of cytochrome P-450, a significant increase in genetic effects was observed. Further experiments, performed by treating cells harvested from logarithmic growth phase in the presence of cytochrome P-450 inhibitors, indicated that the monooxygenase system influenced the genotoxicity of metavanadate while the genetic activity of vanadyl remained unaffected. Aneuploidy effect in the D61M strain of Saccharomyces cerevisiae was induced by either V5 or V4, confirming that vanadium compounds are potentially antitubulin agents in eukaryotic cells. Although these compounds are very toxic in V79 cells, no mutagenic effect was observed in the presence or in the absence of S9 fraction.

摘要

在酿酒酵母的D7和D61M菌株以及中国仓鼠V79细胞系中研究了钒化合物诱导基因活性的能力。在我们之前的工作中,偏钒酸铵(五价形式,V5)在酵母的D7菌株中诱导了有丝分裂基因转换和点回复突变。S9组分的存在降低了遗传毒性,这可能将五价钒还原为四价形式。在本研究中,硫酸氧钒(四价形式,V4)在稳定生长期收获的酵母细胞中未诱导出转化体和回复体。对于对数生长期的酵母细胞(其含有高水平的细胞色素P-450),观察到遗传效应显著增加。通过在细胞色素P-450抑制剂存在下处理对数生长期收获的细胞进行的进一步实验表明,单加氧酶系统影响偏钒酸盐的遗传毒性,而硫酸氧钒的遗传活性不受影响。五价钒(V5)或四价钒(V4)均在酿酒酵母的D61M菌株中诱导了非整倍体效应,证实钒化合物在真核细胞中可能是潜在的抗微管蛋白剂。尽管这些化合物在V79细胞中具有很高的毒性,但在有或没有S9组分存在的情况下均未观察到诱变效应。

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