Daugherty J P
Food Chem Toxicol. 1984 Dec;22(12):951-61. doi: 10.1016/0278-6915(84)90144-3.
The metabolism of butylated hydroxytoluene (BHT) and the effect of BHT on the metabolism of diethylnitrosamine (DEN) was studied in male and female BALB/c mice to further understanding of the selective protection of BHT on the incidence of DEN-induced squamous-stomach carcinomas in female (but not in male) mice. Following intragastric administration of [14C]BHT, the antioxidant was covalently bound to tissue macromolecules. The relative distribution of this bound BHT varied with time; 8 hr after [14C]BHT administration, most of the covalently bound BHT was associated with the protein components; at 96 hr the nucleic acid components bound more BHT than did the protein components. Animals pretreated with BHT and given [14C]DEN intragastrically had lower blood levels of radioactivity and eliminated a larger percentage of DEN and/or its metabolites in the urine and as carbon dioxide than animals given [14C]DEN alone. The binding of DEN and/or its metabolites to cellular macromolecules of the squamous stomach of female animals was decreased following pretreatment with BHT. However, the BHT-associated decrease in DEN binding was also observed in the squamous stomach of male animals and in the liver of both sexes, although the tumour incidence in these target organs for DEN carcinogenesis is not modified by BHT. These results suggest that the BHT-associated decrease in the binding of DEN to DNA is of a generalized rather than a selective nature, and may be insufficient to account for the protective effect of BHT. Two parameters that were found to parallel the susceptibility of DEN target tissues to the anticarcinogenic effects of BHT were the relative degree of inhibition of DEN bound to RNA species and the relative amount of BHT bound to DNA. Thus the anticarcinogenic properties of BHT may be more complex than an induction of enzymes that detoxify the carcinogen and/or an inhibition of enzymes that activate the carcinogen with a resulting decrease in the quantity of carcinogen available for electrophilic reactions.
研究了雄性和雌性BALB/c小鼠中丁基化羟基甲苯（BHT）的代谢以及BHT对二乙基亚硝胺（DEN）代谢的影响，以进一步了解BHT对雌性（而非雄性）小鼠中DEN诱导的鳞状胃癌发病率的选择性保护作用。经胃内给予[14C]BHT后，该抗氧化剂与组织大分子共价结合。这种结合的BHT的相对分布随时间变化；给予[14C]BHT后8小时，大部分共价结合的BHT与蛋白质成分相关；在96小时时，核酸成分结合的BHT比蛋白质成分更多。用BHT预处理并经胃内给予[14C]DEN的动物，其血液中的放射性水平较低，并且与单独给予[14C]DEN的动物相比，在尿液中以及以二氧化碳形式排出的DEN和/或其代谢产物的百分比更高。用BHT预处理后，雌性动物鳞状胃的细胞大分子中DEN和/或其代谢产物的结合减少。然而，在雄性动物鳞状胃以及两性的肝脏中也观察到了与BHT相关的DEN结合减少，尽管BHT并未改变这些DEN致癌作用的靶器官中的肿瘤发生率。这些结果表明，与BHT相关的DEN与DNA结合的减少具有普遍性而非选择性，并且可能不足以解释BHT的保护作用。发现与DEN靶组织对BHT抗癌作用的敏感性平行的两个参数是与RNA种类结合的DEN的相对抑制程度以及与DNA结合的BHT的相对量。因此，BHT的抗癌特性可能比诱导使致癌物解毒的酶和 / 或抑制激活致癌物的酶从而导致可用于亲电反应的致癌物数量减少更为复杂。
