Chadwick R W, George S E, Kohan M J, Williams R W, Allison J C, Talley D L, Hayes Y O, Chang J
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
J Toxicol Environ Health. 1995 Mar;44(3):319-36. doi: 10.1080/15287399509531962.
Pretreatment of male Fischer 344 rats for 5 wk with coal tar creosote, a coal distillation product that is widely used as a wood preservative, potentiated the excretion of urinary mutagens in 2,6-dinitrotoluene (DNT) treated rats. Creosote increased the bioactivation of DNT to significantly greater levels of urinary genotoxic metabolites and/or formed DNA adducts in the liver. A significant increase in the excretion of mutagenic DNT metabolites was observed after the first week of creosote treatment, peaked at wk 3, and then decreased by 33% after 5 wk of treatment. Nevertheless, there was a significant increase (66%) in the formation of DNT-derived DNA adducts in the livers of rats treated with DNT plus creosote at wk 5. Increased cecal beta-glucuronidase activity and reduced small intestinal nitroreductase activity may play roles in the bioactivation of DNT. The excretion of mutagenic DNT metabolites supplies useful information about the bioactivation of DNT; it does not provide a useful index of DNT-derived hepatic DNA adduct formation. Such interactions could be important to predictive risk assessment because the overall cancer risk of such chemical mixtures may exceed the sum of the component risks.
用煤焦油杂酚油对雄性Fischer 344大鼠进行为期5周的预处理，煤焦油杂酚油是一种广泛用作木材防腐剂的煤蒸馏产品，它增强了2,6 -二硝基甲苯（DNT）处理大鼠尿液中诱变剂的排泄。杂酚油增加了DNT的生物活化作用，使其在尿液中产生的遗传毒性代谢物水平显著升高，和/或在肝脏中形成DNA加合物。在杂酚油处理的第一周后，诱变DNT代谢物的排泄量显著增加，在第3周达到峰值，然后在处理5周后下降了33%。然而，在第5周时，用DNT加杂酚油处理的大鼠肝脏中，DNT衍生的DNA加合物形成量显著增加（66%）。盲肠β -葡萄糖醛酸酶活性增加和小肠硝基还原酶活性降低可能在DNT的生物活化中起作用。诱变DNT代谢物的排泄为DNT的生物活化提供了有用信息；但它并不能为DNT衍生的肝脏DNA加合物形成提供有用指标。这种相互作用对于预测性风险评估可能很重要，因为此类化学混合物的总体癌症风险可能超过各成分风险之和。
