George S E, Chadwick R W, Kohan M J, Allison J C, Warren S H, Williams R W
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Environ Mol Mutagen. 1995;26(2):178-84. doi: 10.1002/em.2850260212.
Atrazine (ATZ), an s-triazine herbicide, is a widespread environmental contaminant. The hepatocarcinogenic component of technical grade dinitrotoluene, 2,6-dinitrotoluene (2,6-DNT, 19.5%), is a byproduct of trinitrotoluene synthesis and is found at production sites. This study explores the effect of ATZ treatment on the bioactivation of the promutagen, 2,6-DNT. Male Fischer 344 rats (5 weeks old) were administered 50 mg/kg of ATZ by gavage for 5 weeks. At 1, 3, and 5 weeks, both DMSO-control and ATZ-pretreated rats were treated p.o. with 75 mg/kg of 2,6-DNT and were housed in metabolism cages for urine collection. Sulfatase- and beta-glucuronidase-treated, concentrated urine was bioassayed for urinary mutagens in a microsuspension modification of the Salmonella assay with and without metabolic activation. No significant change in mutagen excretion was observed in ATZ-treated rats; however, an elevation in direct-acting urine mutagens from rats receiving ATZ and 2,6-DNT at weeks 1 (359 +/- 68 vs. 621 +/- 96 revertants/ml) and 5 (278 +/- 46 vs. 667 +/- 109 revertants/ml) of treatment was observed. The increase in production of urinary mutagens was accompanied by an elevation in small intestinal nitroreductase activity. Increases in large intestinal nitroreductase and beta-glucuronidase were observed after 5 weeks. There was no apparent effect of ATZ following 5 weeks of treatment on the production of 2,6-DNT-derived hepatic DNA adducts. ATZ treatment modifies intestinal enzymes responsible for promutagen bioactivation, and potentiates the excretion of mutagenic urine in 2,6-DNT-treated animals.
莠去津（ATZ）是一种均三嗪类除草剂，是一种广泛存在的环境污染物。工业级二硝基甲苯中的肝癌致癌成分2,6-二硝基甲苯（2,6-DNT，含量为19.5%）是三硝基甲苯合成的副产物，在生产场所被发现。本研究探讨了ATZ处理对前诱变剂2,6-DNT生物活化的影响。对5周龄的雄性Fischer 344大鼠经口灌胃给予50 mg/kg的ATZ，持续5周。在第1、3和5周时，用二甲基亚砜（DMSO）对照和经ATZ预处理的大鼠经口给予75 mg/kg的2,6-DNT，并饲养在代谢笼中收集尿液。经硫酸酯酶和β-葡萄糖醛酸酶处理并浓缩的尿液，在有或无代谢活化的情况下，采用沙门氏菌试验的微悬浮改良法对尿中诱变剂进行生物测定。在经ATZ处理的大鼠中未观察到诱变剂排泄的显著变化；然而，在处理第1周（359±68对621±96回复突变体/毫升）和第5周（278±46对667±109回复突变体/毫升）时，观察到接受ATZ和2,6-DNT的大鼠直接作用尿诱变剂有所升高。尿诱变剂产量的增加伴随着小肠硝基还原酶活性的升高。在5周后观察到大肠硝基还原酶和β-葡萄糖醛酸酶增加。在处理5周后，ATZ对2,6-DNT衍生的肝DNA加合物的产生没有明显影响。ATZ处理可改变负责前诱变剂生物活化的肠道酶，并增强2,6-DNT处理动物中诱变尿液的排泄。
