Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.

摘要: Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk hormone-dependent cancers after Cd exposure. The mechanisms underlying these are still under investigation. Our aim was to study the on cellular signaling pathways vivo with special focus estrogen perform benchmark dose analysis effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no organ bw testicular histology, indicating subtoxic exposure levels. transgene luciferase, reporting genomic response, significantly by EE2 but not Cd. However, affected kinase phosphorylation endogenous gene expression. Interestingly, expression changes displayed a traditional dose-response relationship, levels Mt1, Mt2, p53, c-fos, Mdm2 being 92.9, 19.9, 7.6, 259, 25.9 μg/kg bw, respectively, only detected at low Phosphorylation Erk1/2 even lowest group, 0.5 rendering pErk1/2 more sensitive sensor than Collectively, our data that triggered markedly concentration dependent. Furthermore, we conclude estrogen-like likely result from mechanism different steroidal estrogens.