镉致前列腺恶性肿瘤的分子毒理学机制研究

In this study, we found that cadmium administrated by oral or injected by s.c at the carcinogenic doses disrupted serum sex hormone homeostasis (testosterone, follicle stimulating hormone, and luteinizing hormone) and induced/inhibited gene expressions in mRNA levels of hormone receptors (androgen and estrogen receptor), oncogene (c-jun,c-myc) and apoptosis-associated gene (p53, bcl2) in acute and chronic toxicity test of rats. The above cadmium-induced changes might be the main molecular mechanisms of prostate injuries or cancer induced by cadmium. Metallothonein and zinc could be protective effects on the injuries or cancer of prostate. In the largest scale epidemiological studies on environmental and occupational cadmium exposure in China, we found at first time that cadmium exposure in Chinese population could result in damage to human prostate, possibly related to carcinogenesis, and the disruption of serum sex hormone might be related to the cadmium-induced prostate injury.

本课题拟在人群和临床病例检测基础上，采用长期动物实验，通过分子毒理学方法研究镉致前列腺肿瘤过程中对原癌基因、抑癌基因、保护性蛋白基因的异常调控作用的动态变化，以及对细胞凋亡的影响。项目的实施对了解环境镉致前列腺肿瘤的发生机制具有重要的理论和现实意义，同时对发现该类肿瘤的早期监测及疗效的分子生物学指标有重要指导意义。.