Bianchi V, Celotti L, Lanfranchi G, Majone F, Marin G, Montaldi A, Sponza G, Tamino G, Venier P, Zantedeschi A, Levis A G
Mutat Res. 1983 May-Jun;117(3-4):279-300. doi: 10.1016/0165-1218(83)90128-3.
Seven different test systems were utilized to investigate the genetic activity of chromium compounds: infidelity of DNA replication in vitro by DNA pol alpha from calf thymus, damage of DNA detected by alkaline elution in treated mammalian cells or in DNA purified and treated in vitro, DNA repair synthesis in mammalian cells in vitro detected by autoradiography or scintillation counting after labelling with [3H]dThd, gene mutations in the Salmonella typhimurium Ames test, gene mutations (6TG resistance) in cultured hamster cells, sister-chromatid exchanges in different rodent cell cultures, and transformation to anchorage-independent growth of hamster cells in vitro (soft-agar assay). Potassium dichromate and chromium chloride were used as water-soluble Cr(VI) and Cr(III) salts. Several reference mutagens (EMS, MMS, MMC, 4NQO) were included in the single tests as positive controls. Cr(VI) was active in all the tested systems, except in the induction of DNA damage and DNA repair synthesis in cultured cells. Cr(III), on the other hand, was absolutely inactive unless a direct interaction with purified DNA was permitted by the test conditions. The relevance of data from the various tests to the understanding of the mechanisms of the genotoxic activity of chromium is discussed. Effects other than the direct interaction of Cr(III) with DNA are inferred, which can cause infidelity of the DNA polymerase functions.
通过小牛胸腺的DNA聚合酶α体外检测DNA复制的不忠实性;在处理过的哺乳动物细胞中或体外纯化和处理的DNA中,通过碱性洗脱检测DNA损伤;在用[3H]dThd标记后,通过放射自显影或闪烁计数体外检测哺乳动物细胞中的DNA修复合成;在鼠伤寒沙门氏菌艾姆斯试验中检测基因突变;在培养的仓鼠细胞中检测基因突变(6TG抗性);在不同的啮齿动物细胞培养物中检测姐妹染色单体交换;以及在体外检测仓鼠细胞向非贴壁依赖性生长的转化(软琼脂试验)。重铬酸钾和氯化铬被用作水溶性的Cr(VI)和Cr(III)盐。在单项测试中纳入了几种参考诱变剂(EMS、MMS、MMC、4NQO)作为阳性对照。Cr(VI)在所有测试系统中均有活性,但在培养细胞中诱导DNA损伤和DNA修复合成方面除外。另一方面,Cr(III)绝对无活性,除非测试条件允许其与纯化的DNA直接相互作用。讨论了各种测试数据与理解铬的遗传毒性活性机制的相关性。推断出除Cr(III)与DNA直接相互作用之外的其他效应,这些效应可导致DNA聚合酶功能的不忠实性。