Lupulescu A
J Natl Cancer Inst. 1985 Feb;74(2):499-507.
The protective effect of progesterone on the development of chemically induced carcinomas (squamous cell carcinomas in mice and basal cell carcinomas in rats) by 3-methylcholanthrene [(MCA) CAS: 56-49-5] was studied. Progesterone administration decreased the average number, size, and weight of carcinomas by 45-50% as compared to those of tumors treated with MCA alone at any time interval. DNA radioactivity and autoradiographic studies with the use of [3H]thymidine showed an inhibition of DNA synthesis in the neoplastic cell nuclei following a concomitant administration of progesterone and MCA (18.4%) as compared to the DNA synthesis following administration of MCA alone (35.0%). Electron microscopic and cytologic observations revealed salient ultrastructural findings following progesterone administration, with advanced cytolysis, tumefied mitochondria, large populations of secondary lysosomes, and autophagic formations; also, cell differentiation tended to be of a glandular-adenomatoid type following progesterone and MCA administration as compared to the characteristic squamous cell and basal cell carcinomas after treatment with MCA alone. In addition, scanning electron microscopic observations revealed advanced cytolytic areas with several disintegrated neoplastic cells and cell debris intermingled with red blood cells, following progesterone and MCA administration. The present findings demonstrate that progesterone in pharmacologic doses exerts important chemoprotective effects on carcinoma formation, possibly by interfering with MCA metabolism and inhibiting DNA synthesis in the epidermal neoplastic cells, and thus plays an important role in tumorigenesis.
研究了孕酮对3-甲基胆蒽[（MCA），化学物质登记号：56-49-5]诱导的癌（小鼠鳞状细胞癌和大鼠基底细胞癌）发生发展的保护作用。与任何时间间隔单独用MCA处理的肿瘤相比，给予孕酮使癌的平均数量、大小和重量减少了45%-50%。使用[3H]胸腺嘧啶进行的DNA放射性和放射自显影研究表明，与单独给予MCA后DNA合成（35.0%）相比，同时给予孕酮和MCA后肿瘤细胞核中的DNA合成受到抑制（18.4%）。电子显微镜和细胞学观察显示，给予孕酮后有显著的超微结构发现，包括细胞溶解加剧、线粒体肿胀、大量次级溶酶体和自噬形成；此外，与单独用MCA处理后特征性的鳞状细胞癌和基底细胞癌相比，给予孕酮和MCA后细胞分化倾向于腺腺瘤样类型。另外，扫描电子显微镜观察显示，给予孕酮和MCA后有细胞溶解加剧的区域，有几个解体的肿瘤细胞和细胞碎片与红细胞混合在一起。目前的研究结果表明，药理剂量的孕酮对癌的形成具有重要的化学保护作用，可能是通过干扰MCA代谢和抑制表皮肿瘤细胞中的DNA合成，从而在肿瘤发生中发挥重要作用。
