Sinha D K, Dao T L
J Natl Cancer Inst. 1980 Mar;64(3):519-21.
Two routes of administration were used to test the susceptibility of the mammary gland of the rat to 7,12-dimethylbenz[a]anthracene (DMBA) carcinogenesis in relation to age of the tissue. In one series of experiments, 60-, 70-, 90-, 120-, 150-, and 200-day-old female noninbred Sprague-Dawley rats were given DMBA iv. In parallel experiments, rats of the same ages as those above were given DMBA by local application. Mammary tumors developed in 80-90% of the 60- and 70-day-old rats and in 40% of the 90-day-old rats. Rats 120 days old and older were completely "refractory" to DMBA. In contrast, all rats, irrespective of their ages, developed tumors when DMBA was applied locally. The DNA synthesis labeling index (LI) of mammary glands of rats in two series of experiments was examined by [3H]thymidine incorporation and autoradiography at 24, 48, and 72 hours after DMBA treatment. DMBA, given iv significantly inhibited DNA synthesis in mammary glands, but DMBA applied locally significantly increased the LI of the mammary glands. Thus the LI of the mammary glands in 60-day-old rats increased from 8% (control, untreated) to 16% (rats receiving local applications of DMBA), whereas the LI of the mammary glands in 150-day-old rats increased from 1.15% (control, untreated) to 8% (rats receiving local application of DMBA).
采用两种给药途径来测试大鼠乳腺对7,12-二甲基苯并[a]蒽（DMBA）致癌作用的易感性，该易感性与组织年龄有关。在一系列实验中，给60日龄、70日龄、90日龄、120日龄、150日龄和200日龄的非近交雌性Sprague-Dawley大鼠静脉注射DMBA。在平行实验中，给与上述相同年龄的大鼠局部应用DMBA。80%-90%的60日龄和70日龄大鼠发生了乳腺肿瘤，90日龄大鼠中有40%发生了乳腺肿瘤。120日龄及以上的大鼠对DMBA完全“耐受”。相比之下，当局部应用DMBA时，所有大鼠无论年龄大小均发生了肿瘤。在DMBA处理后24、48和72小时，通过[3H]胸腺嘧啶核苷掺入和放射自显影检查了两个系列实验中大鼠乳腺的DNA合成标记指数（LI）。静脉注射DMBA显著抑制了乳腺中的DNA合成，但局部应用DMBA显著增加了乳腺的LI。因此，60日龄大鼠乳腺的LI从8%（对照，未处理）增加到16%（接受局部应用DMBA的大鼠），而150日龄大鼠乳腺的LI从1.15%（对照，未处理）增加到8%（接受局部应用DMBA的大鼠）。
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