AIM:Rodent testes are generally more susceptible tocadmium (Cd)-induced toxicity than liver.To clarify themolecular mechanism of Cd-induced toxicity in testes,wecompared metallothionein (MT) gene expression,MT proteinaccumulation,and Cd retention at different time in freshlyisolated testicular interstitial cells and liver of rats treatedwith Cd.METHODS:Adult male Sprague-Dawley rats weighing 250-280 g received a s.c injection of 4.0 μmol Cd/kg and wereeuthanized by CO_2 asphyxiation 1 h,3 h,6 h,or 24 h later.Tissue was sampled and testicular interstitial cells wereisolated.There were three replicates per treatment and 3animals per replicate for RNA analyses,others,threereplicates per treatment and one animal per replicate.MT1and MT2 mRNA levels were determined by semi-quantitativeRT-PCR analysis followed by densitometry scanning,andMT was estimated by the enzyme-linked immunosorbentassay (ELISA) method.Cadmium content was determinedby atomic absorption spectrophotometry.The sameparametersd were also analyzed in the liver,since this tissueunquestionably accumulate MT.RESULTS:The rat testis expressed MT1 and MT2,the majorisoforms.We also found that untreated animals containedrelatively high basal levels of both isoform mRNA,whichwere increased after Cd treatment in liver and peaked at 3 h,followed by a decline.In contrast,the mRNA levels ininterstitial cells peaked at 6 h.Interestingly,the induction ofMT1 mRNA was lower than MT2 mRNA in liver of rat treatedwith Cd,but it was opposite to interstitial cells.Cd exposuresubstantially increased hepatic MT (3.9-fold increase),butdid not increase MT translation in interstitial cells.CONCLUSION:Cd-induced expression of MT isoforms isnot only tissue dependent but also time-dependent.Theinability to induce the metal-detoxicating MT-protein inresponse to Cd,may account for a higher susceptibility oftestes to Cd toxicity and carcinogenesis compared to liver. AIM: Rodent testes are generally more susceptible tocadmium (Cd) -induced toxicity than liver. Clarifying themolecular mechanism of Cd-induced toxicity in testes, wecompared metallothionein (MT) gene expression, MT proteinaccumulation, and Cd retention at different time in freshlyisolated testicular interstitial cells and liver of rats treated with Cd.METHODS: Adult male Sprague-Dawley rats weighing 250-280 g received a sc injection of 4.0 μmol Cd / kg and wereeuthanized by CO_2 asphyxiation 1 h, 3 h, 6 h, or 24 h later Tissue was sampled and testicular interstitial cells wereisolated. There were three replicates per treatment and 3 animals per replicate for RNA analyzes, others, three replicates per treatment and one animal per replicate. MT1 and MT2 mRNA levels were determined by semi-quantitative RT-PCR analysis followed by densitometry scanning, and MT was estimated by the enzyme-linked immunosorbent assay (ELISA) method. Cadmium content was determined by atomic absorption spectrophotometry. sameparame Since the tissue is highly accumulate in the liver, since this tissue is highly accumulate MT.RESULTS: The rat testis was expressed MT1 and MT2, the major isoforms. We also found that untreated animals contained relatively high basal levels of both isoform mRNA, which were increased after Cd treatment in liver and peaked at 3 h followed by a decline. Contrast, the mRNA levels ininterstitial cells peaked at 6 h. Interestingly, the induction of MT1 mRNA was lower than MT2 mRNA in liver of rat treated with Cd, but it was opposite to interstitial cells. Cd exposuresubstantially increased hepatic MT (3.9-fold increase), butdid not increase MT translation in interstitial cells. CONCLUSION: Cd-induced expression of MT isoforms is not only tissue dependent but also time-dependent. The ability to induce the metal-detoxicating MT-protein inresponse to Cd, may account for a higher susceptibility oftes to Cd toxicity and carcinogenesis compared to liver.