Inhibition of 8-hydroxyguanine repair in testes after administration of cadmium chloride to GSH-depleted rats.
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.
Hirano
T
T
Department of Environmental Oncology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Fukuoka, Yahatanishi-ku, Kitakyushu, 807, Japan.
Yamaguchi
Y
Y
Kasai
H
H
D000818:Animals; D019328:Buthionine Sulfoximine; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004260:DNA Repair; D004791:Enzyme Inhibitors; D005978:Glutathione / Q000172:deficiency*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D002273:Carcinogens; D004791:Enzyme Inhibitors; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D013482:Superoxide Dismutase; D005978:Glutathione; D019256:Cadmium Chloride