Welsch C W, DeHoog J V
Department of Anatomy, Michigan State University, East Lansing 48824.
Cancer Res. 1988 Apr 15;48(8):2074-7.
The effect of caffeine (430-500 mg/liter of drinking water) on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a chemically defined diet containing standard (5%) or high (20%) levels of fat (corn oil) was examined. In the initiation studies, caffeine and the standard or high fat diet treatments were provided for 34 days, from 24-29 days of age to 58-63 days of age. Three days prior to termination of caffeine-fat diet treatments, each rat received a single dose of DMBA. In the promotion studies, caffeine and the standard or high fat diets were provided commencing 3 days after a single dose of DMBA (at 56-61 days of age) and until termination of the study. Caffeine consumption, during the initiation phase significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat), in rats fed either a standard or high fat diet. In the promotion studies, prolonged consumption of caffeine in rats fed either a standard or high fat diet did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, an apparent increase in mammary carcinoma multiplicity was observed; this increase in mammary carcinoma multiplicity did not, however, reach the 5% level of statistical probability. When caffeine was administered during both the initiation and promotion phases, no significant effect on mammary carcinoma multiplicity was observed. Treatment of rats during the initiation or promotion phases with caffeinated coffee (via drinking water) mimicked the mammary tumor modulating activities of caffeine. Decaffeinated coffee consumption did not effect either the initiation or promotion phases of this tumorigenic process. In both the initiation and promotion studies, caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of mammary tumor appearance. Thus, in female rats fed a chemically defined standard or high fat diet, caffeine consumption can significantly influence chemical carcinogenesis of the mammary gland; an effect that is dependent upon the duration and time-span of caffeine administration.
研究了咖啡因（430 - 500毫克/升饮用水）对雌性斯普拉格 - 道利大鼠乳腺肿瘤发生起始和促进阶段的影响，这些大鼠食用含有标准（5%）或高脂肪（20%）（玉米油）的化学定义饮食，且用7,12 - 二甲基苯并(a)蒽（DMBA）诱导乳腺肿瘤。在起始研究中，从24 - 29日龄至58 - 63日龄，给予大鼠咖啡因以及标准或高脂肪饮食处理，为期34天。在终止咖啡因 - 脂肪饮食处理前3天，每只大鼠接受单剂量的DMBA。在促进研究中，在单剂量DMBA给药后3天（56 - 61日龄）开始给予大鼠咖啡因以及标准或高脂肪饮食，直至研究结束。在起始阶段，食用咖啡因显著（P小于0.05）降低了食用标准或高脂肪饮食大鼠的乳腺癌多发性（肿瘤数量/大鼠）。在促进研究中，食用标准或高脂肪饮食的大鼠长期摄入咖啡因对乳腺癌多发性没有显著影响。在促进的早期阶段，观察到乳腺癌多发性有明显增加；然而，这种乳腺癌多发性的增加未达到5%的统计学概率水平。当在起始和促进阶段都给予咖啡因时，未观察到对乳腺癌多发性有显著影响。在起始或促进阶段用含咖啡因的咖啡（通过饮用水）处理大鼠，模拟了咖啡因对乳腺肿瘤的调节活性。饮用脱咖啡因咖啡对这个致癌过程的起始或促进阶段均无影响。在起始和促进研究中，摄入咖啡因和/或咖啡对乳腺癌的发生率（患乳腺癌大鼠的百分比）或乳腺肿瘤出现的平均潜伏期均无显著影响。因此，在食用化学定义的标准或高脂肪饮食的雌性大鼠中，摄入咖啡因可显著影响乳腺的化学致癌作用；这种影响取决于咖啡因给药的持续时间和时间跨度。
