Testosterone Treatment Is a Potent Tumor Promoter for the Rat Prostate
Testosterone Treatment Is a Potent Tumor Promoter for the Rat Prostate
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DOI：
10.1210/en.2014-1688
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发表时间：
2014-12-01
期刊：
影响因子：
4.8
通讯作者：
Bosland, Maarten C.
中科院分区：
文献类型：
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作者：
Bosland, Maarten C.
睾丸激素越来越多地用于中年和老年男性，但这种治疗的安全性受到质疑，并且前列腺癌的可能风险尚不清楚。我们通过缓释硅橡胶植入物对 Wistar Cpb: WU 大鼠进行长期治疗，其中睾酮剂量以剂量相关的方式增加循环水平，无论是否预先注射致癌物质 N-亚硝基-N-甲基脲 (MNU)。如果没有 MNU，睾酮会在 10%-18% 的大鼠中诱发前列腺癌，注射 MNU 后，睾酮治疗会在 50%-71% 的大鼠中诱发前列腺癌，剂量反应非常陡峭，即使在不提高循环睾酮水平的睾酮剂量下，前列腺肿瘤发病率也达到 50%。接受 MNU 或未治疗的大鼠不会发生前列腺癌，而单独使用睾酮可降低前列腺癌的发病率，并增加其他部位携带肿瘤（尤其是恶性肿瘤）的大鼠数量。因此，在本研究中，睾酮被证明是一种弱的完全致癌物，并且是大鼠前列腺的强肿瘤促进剂。这些发现对男性使用睾酮疗法具有潜在的重大公共卫生影响。
Testosterone is increasingly prescribed to middle aged and older men, but the safety of this treatment has been called into question, and the possible risk of prostate cancer is unknown. We treated Wistar Cpb: WU rats chronically via slow-release Silastic implants with doses of testosterone that increased circulating levels in a dose-related fashion with or without a preceding single injection of the carcinogen N-nitroso-N-methylurea (MNU). Without MNU, testosterone induced prostate carcinomas in 10%-18% of rats, and after MNU injection, testosterone treatment caused prostate cancer in 50%-71% of rats with a very steep dose response, producing a 50% prostatic tumor incidence even at a testosterone dose that did not elevate circulating testosterone levels. Prostate cancers did not occur in rats given MNU or no treatment, whereas testosterone alone induced a low incidence of prostate cancer and increased the number rats bearing tumors at other sites, particularly malignant tumors. Thus, testosterone was shown to be a weak complete carcinogen and a strong tumor promoter for the rat prostate in this study. These findings have potential significant public health implications for the use of testosterone therapy in men.