Cytotoxic effects of hexavalent and trivalent chromium on mammalian cells in vitro.

Cytotoxic effects of hexavalent and trivalent chromium on mammalian cells in vitro.
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六价和三价铬在体外对哺乳动物细胞的细胞毒性作用。

DOI:
10.1038/bjc.1978.58
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发表时间:
1978-03
影响因子:
8.8
通讯作者:
Pegoraro, B
Pegoraro, B
中科院分区:
医学1区
文献类型:
--
作者:
Levis, A G;Bianchi, V;Tamino, G;Pegoraro, B

文献摘要

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研究了六价(k2Cr2O7)和三价(CrCl3)铬化合物对培养的仓鼠成纤维细胞(BHK系)和人上皮样细胞(HEp系)的细胞毒性作用。K2Cr2O7刺激标记胸苷进入可溶性细胞内池的摄取(核苷摄取的刺激代表Cr6+的特定作用),而Cr3+总是发挥抑制作用。DNA合成受到两种铬化合物的抑制,尤其是K2Cr2O7。此外,有效的CrCl3浓度降低了DNA和RNA对高氯酸水解的敏感性。k2Cr2O7在平衡盐溶液中处理,其中Cr6+还原不明显,诱导比在完全生长培养基中处理更明显的细胞毒性作用。HEp细胞比BHK成纤维细胞对K2Cr2O7更敏感:前者对TdR摄取的刺激更小,DNA合成和细胞存活受到更大影响。BHK细胞对K2Cr2O7的存活表明了细胞失活的多打击机制,外推数约为10。根据处理溶液和处理细胞中Cr的定量测定,Cr的细胞毒性作用归因于质膜水平上Cr6+对核苷摄取机制的作用,以及细胞内Cr3+与DNA分子上的亲核靶点的相互作用。
The cytotoxic effects of hexavalent (k2Cr2O7) and trivalent (CrCl3) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line). K2Cr2O7 stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr6+) while Cr3+ always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K2Cr2O7. Moreover, the effective CrCl3 concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k2Cr2O7 in balanced salt solution, where Cr6+ reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium. HEp cells turned out to be more sensitive to K2Cr2O7 than BHK fibroblasts: in the former line TdR uptake is less stimulated, DNA synthesis and cell survival are more affected. Survival of BHK cells to K2Cr2O7 indicates a multi-hit mechanism of cell inactivation, the extrapolation number being about 10. On the basis of quantitative Cr determinations in the treatment solutions and in the treated cells, the cytotoxic effects of Cr are attributed to the action of Cr6+ at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr3+ at the intracellular level with nucleophilic targets on the DNA molecule.