Moon R C, Grubbs C J, Sporn M B
Cancer Res. 1976 Jul;36(7 PT 2):2626-30.
The administration of 2.5 mg retinyl acetate daily in the diet to female Sprague-Dawley rats beginning 7 days after the intragastric instillation of either 2.5, 5, or 15 mg 7,12-dimethylbenz(a)anthracene (CMBA) resulted in a reduction in the incidence of benign mammary tumors of 37, 30, and 31%, respectively. An equally significant reduction in the number of tumors was also evident. Although no difference was noted in the percentage incidence of mammary adenocarcinomas between the placebo and 2.5 mg retinyl acetate-treated groups at the 2.5-mg DMBA level, the percentage incidence was reduced by 52 and 39% in these groups at the 5- and 15-mg DMBA dose. Furthermore, the number of adenocarcinomas was also significantly reduced. Although both the percentage incidence and number of tumors were reduced by treatment with 1 mg retinyl acetate, these differences were not statistically significant. Liver histology and liver function tests of rats of the retinyl acetate groups did not differ from that of the control group. Similarly, the estrus cycle of treated animals did not differ from that of control rats. These data indicate that relatively large doses of retinyl acetate significantly inhibit the development of DMBA-induced mammary adenocarcinomas and benign tumors. Furthermore, the suppression of mammary tumorigenesis is apparently not the result of an alteration in either the metabolism of DMBA or estrogen nor to an inhibition of tumor growth resulting from retinyl acetate toxicity. The inhibitory effect of retinyl acetate may be related to the effect of retinoids on epithelial cell differentiation and/or reversal of carcinogen-induced anaplasia.
在雌性斯普拉格 - 道利大鼠胃内滴注2.5、5或15毫克7,12 - 二甲基苯并(a)蒽（DMBA）7天后，开始在其饮食中每日给予2.5毫克醋酸视黄酯，结果良性乳腺肿瘤的发生率分别降低了37%、30%和31%。肿瘤数量同样显著减少。虽然在2.5毫克DMBA剂量水平下，安慰剂组和2.5毫克醋酸视黄酯治疗组之间乳腺腺癌的发生率百分比没有差异，但在5毫克和15毫克DMBA剂量下，这些组的发生率百分比分别降低了52%和39%。此外，腺癌的数量也显著减少。虽然用1毫克醋酸视黄酯治疗可降低肿瘤的发生率百分比和数量，但这些差异无统计学意义。醋酸视黄酯组大鼠的肝脏组织学和肝功能测试与对照组无差异。同样，治疗动物的发情周期与对照大鼠也无差异。这些数据表明，相对大剂量的醋酸视黄酯可显著抑制DMBA诱导的乳腺腺癌和良性肿瘤的发展。此外，乳腺肿瘤发生的抑制显然不是DMBA或雌激素代谢改变的结果，也不是醋酸视黄酯毒性导致肿瘤生长抑制的结果。醋酸视黄酯的抑制作用可能与类视黄醇对上皮细胞分化的作用和/或致癌物诱导的间变逆转有关。
