Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats.
Apoptosis and a change in the expression of p53, c-jun and MT-I genes occurred in rats exposed to cadmium in a way known to cause carcinogenesis in testes and ventral prostate. In situ end labelling (ISEL), DNA electrophoresis, and RT-PCR methods were used in present study. Adult male Wistar rats were given a single (s.c.) injection of 0, 5, 10, or 20 micromol/kg CdCl2. Then 12, 48 or 96 h after administration of cadmium, animals were sacrificed. It was observed that cadmium markedly induced apoptosis in the testes at the dose of 5 micromol/kg while 10 and 20 micromol/kg cadmium caused more necrosis than apoptosis. Apoptosis in the ventral prostate was markedly induced by all the doses of cadmium and there was an obvious time- and dose-dependent relationship between apoptotic index (AI) and cadmium treatment. Far fewer apoptotic cells appeared in liver, compared to the testes and ventral prostate. p53 mRNA expression was clearly enhanced in the ventral prostate but clearly suppressed in the testes by cadmium exposure, and the time- and dose-effect was very clear. The expression level of p53 in the liver was not affected by cadmium treatment. Cadmium-induced overexpression of c-jun gene appeared at 12 h in the liver, but not until 96 h in the testes and ventral prostate. Although the MT-I gene was found to be expressed in all tissues, marked induction by cadmium of the expression of MT-I gene was only observed in the liver. These results indicate: (1) that apoptosis is an early mechanism of acute tissue damage by cadmium in the testes and ventral prostate; (2) that p53 and c-jun genes may be involved in cadmium-induced cytotoxicity (apoptosis) and related carcinogenicity in male reproductive tissues; and (3) that the enhanced expression of MT-I in the liver could protect this organ from cadmium-induced cytotoxicity (apoptosis) and carcinogenicity.
Zhou
T
T
Department of Environmental Medicine, Umea University, Sweden.
Zhou
G
G
Song
W
W
Eguchi
N
N
Lu
W
W
Lundin
E
E
Jin
T
T
Nordberg
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein