Hirano T, Yamaguchi Y, Kasai H
Department of Environmental Oncology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Fukuoka, Yahatanishi-ku, Kitakyushu, 807, Japan.
Toxicol Appl Pharmacol. 1997 Nov;147(1):9-14. doi: 10.1006/taap.1997.8260.
The main goal of this study is to investigate the mechanism of cadmium (Cd)-induced carcinogenesis by reactive oxygen species. Rats were divided into four groups and were treated with (i) saline (control), (ii) cadmium chloride (CdCl2), (iii) l-buthionine-[S, R]-sulfoximine (BSO, an inhibitor of GSH biosynthesis), and (iv) CdCl2 and BSO, respectively. They were euthanized at 0, 24, 48, and 72 hr after these treatments, and the lungs and testes were analyzed. After treatment with both CdCl2 and BSO, the testicular 8-OH-Gua level increased (48 hr), its repair activity decreased (48 and 72 hr), the GSH content was markedly suppressed (48 and 72 hr), the superoxide dismutase activities slightly (48 and 72 hr) decreased, and the lipid peroxidation level increased (24 and 72 hr) in the testes as compared to the control levels. These results suggest that under GSH-depleted conditions, CdCl2 inhibits 8-OH-Gua repair activity in the rat testis and 8-OH-Gua accumulates in the DNA, which may pertain to testicular carcinogenesis.
本研究的主要目的是探究活性氧介导的镉（Cd）致癌机制。将大鼠分为四组，分别用（i）生理盐水（对照组）、（ii）氯化镉（CdCl₂）、（iii）L-丁硫氨酸-[S,R]-亚砜亚胺（BSO，谷胱甘肽生物合成抑制剂）和（iv）CdCl₂与BSO进行处理。在这些处理后的0、24、48和72小时将它们安乐死，并对肺和睾丸进行分析。与对照组相比，用CdCl₂和BSO处理后，睾丸中8-羟基鸟嘌呤（8-OH-Gua）水平升高（48小时），其修复活性降低（48和72小时），谷胱甘肽（GSH）含量显著受到抑制（48和72小时），超氧化物歧化酶活性略有降低（48和72小时），脂质过氧化水平升高（24和72小时）。这些结果表明，在GSH耗竭的条件下，CdCl₂抑制大鼠睾丸中8-OH-Gua的修复活性，并且8-OH-Gua在DNA中积累，这可能与睾丸致癌有关。
