Verma A K, Johnson J A, Gould M N, Tanner M A
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Cancer Res. 1988 Oct 15;48(20):5754-8.
The effects of dietary supplementation of flavonol quercetin on both 7,12-dimethylbenz(a)anthracene (DMBA)- and N-nitrosomethylurea-induced mammary cancer in female Sprague-Dawley rats were determined. Quercetin diet was started 1 wk before intragastric instillation of DMBA (65 mg/kg of body weight) or i.v. injection of N-nitrosomethylurea (50 mg/kg of body weight) and was continued during the entire period (20 wk) of the experiment. Dietary quercetin inhibited both the incidence and the number of palpable rat mammary tumors; rats fed on 2% quercetin had 25% less incidence of mammary cancer, while the average number of mammary tumors per rat was reduced by 39% at 20 wk post-DMBA administration compared to animals on a control diet. In a separate experiment, a 5% quercetin diet elicited a greater inhibitory effect on the induction of rat mammary tumors by DMBA than was observed with a 2% quercetin diet. The inhibitory effect of quercetin on mammary tumor incidence in rats on 2% and 5% diets and on tumor multiplicity in animals on a 5% diet was statistically significant (P less than 0.05). In addition, the risk of the development of a palpable tumor (as determined by the nonparametric estimate of the hazard function) in the quercetin-fed group was lower than the group on control diet throughout the course of the experiment. Furthermore, 5% dietary quercetin significantly inhibited (P less than 0.05), although to a lesser extent than observed in DMBA-induced tumor formation, both the incidence and the number of palpable mammary tumors per rat induced by N-nitrosomethylurea. Dietary quercetin did not elicit any detectable sign of toxicity. The gain in body weight in rats on the quercetin diet and the quantity of diet consumed per rat per week were similar to those for rats on the control diet.
研究了膳食补充黄酮醇槲皮素对雌性斯普拉格-道利大鼠经7,12-二甲基苯并(a)蒽(DMBA)和N-亚硝基甲脲诱导的乳腺癌的影响。在经胃内灌注DMBA(65毫克/千克体重)或静脉注射N-亚硝基甲脲(50毫克/千克体重)前1周开始给予槲皮素饮食,并在整个实验期间(20周)持续给予。膳食槲皮素抑制了可触及的大鼠乳腺肿瘤的发生率和数量;喂食2%槲皮素的大鼠乳腺癌发生率降低了25%,而与喂食对照饮食的动物相比,在给予DMBA后20周时,每只大鼠的乳腺肿瘤平均数量减少了39%。在另一项实验中,5%槲皮素饮食对DMBA诱导的大鼠乳腺肿瘤的抑制作用比2%槲皮素饮食更明显。槲皮素对2%和5%饮食组大鼠乳腺肿瘤发生率以及5%饮食组动物肿瘤多样性的抑制作用具有统计学意义(P小于0.05)。此外,在整个实验过程中,喂食槲皮素组出现可触及肿瘤的风险(由风险函数的非参数估计确定)低于对照饮食组。此外,5%膳食槲皮素虽然抑制程度低于DMBA诱导的肿瘤形成,但对N-亚硝基甲脲诱导的每只大鼠可触及乳腺肿瘤的发生率和数量均有显著抑制作用(P小于0.05)。膳食槲皮素未引发任何可检测到的毒性迹象。喂食槲皮素饮食的大鼠体重增加以及每只大鼠每周的饮食摄入量与喂食对照饮食的大鼠相似。