Welsch C W, DeHoog J V
Cancer Res. 1983 Feb;43(2):585-91.
Female Sprague-Dawley rats were treated at 53 days of age with a single intubation of 7,12-dimethylbenzanthracene (DMBA). Three days after carcinogen treatment, the animals were treated with retinyl acetate (RA) (at 3 dietary levels), hormone inhibition (HI) [tamoxifen (1-rho-beta-dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene) plus 2 bromo-alpha-ergocryptine], and/or immune stimulation (methanol-extracted residue of Bacillus Calmette-Guérin, cell wall skeleton of Nocardia rubra, or cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant). RA at 0.6 or 1.0 mM concentrations per kg diet significantly reduced the incidence of mammary carcinomas; 0.2 mM concentrations of RA per kg diet did not affect tumor incidence. HI also significantly decreased mammary carcinoma incidence, an effect which was significantly enhanced by all 3 dietary levels of RA. Immune stimulation by methanol-extracted residue of Bacillus Calmette-Guérin or cell wall skeleton of Nocardia rubra did not affect mammary carcinoma incidence when administered either alone or in combination with RA and/or HI. The cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant significantly reduced mammary carcinoma incidence in rats fed RA but did not affect mammary carcinoma incidence in placebo-fed rats or in rats treated only with HI. However, in rats treated with the triple combination of cell particulate of DMBA-induced rat mammary carcinomas plus Freund's complete adjuvant, RA, and HI, no mammary carcinomas were observed for the duration of treatment (20 weeks after DMBA administration). Although HI was always superior to RA feeding in the prophylaxis of this neoplastic process, a significant synergism between these two treatments was consistently observed. This distinct synergism was observed even when using the low dietary level of RA, an amount of RA which by itself was ineffective in the suppression of mammary carcinogenesis. With but one exception, immune stimulation did not significantly influence this carcinogenic process, either when administered alone or when administered to rats with a reduced mammary carcinoma burden, i.e., animals treated with RA and/or HI.
53日龄的雌性斯普拉格-道利大鼠经单次插管给予7,12-二甲基苯并蒽（DMBA）。致癌剂处理三天后，动物接受醋酸视黄酯（RA）（三种饮食水平）、激素抑制（HI）[他莫昔芬（1-ρ-β-二甲基氨基乙氧基苯基-反式-1,2-二苯基丁-1-烯）加2-溴-α-麦角隐亭]和/或免疫刺激（卡介苗甲醇提取物、红色诺卡氏菌细胞壁骨架或DMBA诱导的大鼠乳腺癌细胞颗粒加弗氏完全佐剂）。每千克饮食中浓度为0.6或1.0 mM的RA显著降低了乳腺癌的发病率；每千克饮食中0.2 mM浓度的RA对肿瘤发病率没有影响。HI也显著降低了乳腺癌的发病率，这一效果在所有三种饮食水平的RA作用下均显著增强。单独给予或与RA和/或HI联合给予卡介苗甲醇提取物或红色诺卡氏菌细胞壁骨架进行免疫刺激，均不影响乳腺癌发病率。DMBA诱导的大鼠乳腺癌细胞颗粒加弗氏完全佐剂显著降低了喂食RA大鼠的乳腺癌发病率，但不影响喂食安慰剂大鼠或仅接受HI处理大鼠的乳腺癌发病率。然而，在用DMBA诱导的大鼠乳腺癌细胞颗粒加弗氏完全佐剂、RA和HI三联组合处理的大鼠中，在治疗期间（DMBA给药后20周）未观察到乳腺癌。尽管在预防这种肿瘤形成过程中HI总是优于喂食RA，但始终观察到这两种治疗之间存在显著的协同作用。即使使用低饮食水平的RA，即本身对抑制乳腺癌发生无效的RA量，也观察到了这种明显的协同作用。除了一个例外，免疫刺激单独给予或给予乳腺癌负担减轻的大鼠（即接受RA和/或HI处理的动物）时，均未显著影响这一致癌过程。
