Harvey Philip W, Everett David J, Springall Christopher J
Department of Toxicology, Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire, UK.
J Psychopharmacol. 2008 Mar;22(2 Suppl):20-7. doi: 10.1177/0269881107082624.
Drugs and chemicals shown to induce mammary carcinogenesis in the rat/rodent via prolactin excess have traditionally been argued to pose little or no risk to humans in a regulatory toxicology context. The basis for this assumption is reviewed and placed into context with new evidence in humans that prolactin may be a tumour promoter in the breast and prostate. This evidence includes epidemiology, patient studies involving endocrine evaluation and molecular biology in human cells. It is concluded that hyperprolactinaemia is associated with an increase in breast cancer risk in both post and premenopausal women, that rat carcinogenicity studies are predictive of the human response, and that in a regulatory toxicology context prolactin-induced mammary tumours from nongenotoxic drugs and chemicals are an adverse effect that should not be ignored. More evidence is required concerning prostate cancer risk but molecular biology indicates that prolactin also induces prostate cell proliferation and inhibits apoptosis, which are similar to the responses observed in breast cancer cells.
传统观点认为，在监管毒理学背景下，那些经证实可通过泌乳素过量在大鼠/啮齿动物中诱发乳腺癌的药物和化学物质，对人类几乎不构成风险或没有风险。本文回顾了这一假设的依据，并结合人类的新证据进行了阐述，这些新证据表明泌乳素可能是乳腺和前列腺的肿瘤促进因子。这些证据包括流行病学、涉及内分泌评估的患者研究以及人类细胞中的分子生物学研究。研究得出结论，高泌乳素血症与绝经后和绝经前女性患乳腺癌风险的增加相关，大鼠致癌性研究可预测人类的反应，并且在监管毒理学背景下，非基因毒性药物和化学物质诱发的泌乳素相关乳腺肿瘤是一种不应被忽视的不良反应。关于前列腺癌风险还需要更多证据，但分子生物学表明泌乳素也会诱导前列腺细胞增殖并抑制细胞凋亡，这与在乳腺癌细胞中观察到的反应相似。
