Singletary K W, Nelshoppen J M
Division of Nutritional Sciences, University of Illinois, Urbana-Champaign 61801.
Carcinogenesis. 1991 Oct;12(10):1967-9. doi: 10.1093/carcin/12.10.1967.
The in vivo formation of specific 7,12-dimethylbenz[a]-anthracene (DMBA)-DNA adducts in the mammary gland of the female Sprague-Dawley rat was studied in response to dietary butylated hydroxytoluene (BHT). Dietary BHT concentrations of 0.4 and 0.8% significantly inhibited total DMBA-DNA binding by 41.5 and 35.6% respectively, as compared to controls. However, the decrease in total binding associated with intake of BHT was not due to a uniform inhibition in the formation of all individual adducts. The formation of two adducts resulting from the binding of the anti-dihydrodiolepoxide of DMBA to deoxyguanosine (anti-dGuo) was significantly decreased by a combined average of 51.5% for rats fed BHT-supplemented diets as compared to controls. However, syn-derived DMBA-DNA adducts were not consistently inhibited by dietary BHT. Adduct formation resulting from the binding of the syn-dihydrodiolepoxide of DMBA to deoxyadenosine (syn-dAdo) was significantly inhibited only for rats fed a diet supplemented with 0.4% BHT. The formation of the syn-dGuo adduct was not affected by the feeding of BHT-supplemented diets. These results suggest that in vivo inhibition by BHT of mammary DNA adducts formed from the anti-diastereomer of DMBA may be an important contribution to the inhibitory effect of BHT on the initiation stage of DMBA-induced mammary carcinogenesis.
研究了雌性斯普拉格 - 道利大鼠乳腺中特定的7,12 - 二甲基苯并[a]蒽（DMBA）-DNA加合物的体内形成情况，以响应膳食中的丁基化羟基甲苯（BHT）。与对照组相比，膳食中BHT浓度为0.4%和0.8%时，分别显著抑制总DMBA - DNA结合41.5%和35.6%。然而，与摄入BHT相关的总结合减少并非由于对所有单个加合物形成的均匀抑制。与对照组相比，喂食补充BHT饮食的大鼠中，由DMBA的反式二氢二醇环氧化物与脱氧鸟苷（anti - dGuo）结合产生的两种加合物的形成平均显著降低了51.5%。然而，膳食BHT并未始终抑制顺式衍生的DMBA - DNA加合物。仅对于喂食补充0.4%BHT饮食的大鼠，由DMBA的顺式二氢二醇环氧化物与脱氧腺苷（syn - dAdo）结合产生的加合物形成受到显著抑制。顺式 - dGuo加合物的形成不受补充BHT饮食喂养的影响。这些结果表明，BHT对由DMBA的反式非对映体形成的乳腺DNA加合物的体内抑制作用可能是BHT对DMBA诱导的乳腺癌发生起始阶段抑制作用的重要贡献。
