Nelson G M, Swank A E, Brooks L R, Bailey K C, George S E
U. S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Environmental Carcinogenesis Division, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2001 Apr;60(2):232-41. doi: 10.1093/toxsci/60.2.232.
Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their biologically active forms. The present study was designed to investigate the influence of the cecal microbiota on the mutagenicity of haloacetic acids, and to look at changes in the microbiota populations and enzyme activities associated with exposure to haloacetic acids. PYG medium containing 1 mg/ml of monochloroacetic (MCA), monobromoacetic (MBA), dichloroacetic (DCA), dibromoacetic (DBA), trichloroacetic (TCA), tribromoacetic (TBA), or bromochloroacetic (BCA) acid was inoculated with rat cecal homogenate and incubated anaerobically at 37 degrees C. Growth curves were performed with enumeration of the microflora populations on selective media. Mutagenicity in a Salmonella microsuspension bioassay was determined after incubation for various lengths of time, with or without the cecal microbiota. At 15 h of incubation, enzyme assays determined the activities for beta-glucuronidase, beta-galactosidase, beta-glucosidase, azoreductase, nitroreductase, dechlorinase, and dehydrochlorinase. The haloacetic acids, with the exception of BCA, were toxic to the cecal microbiota, and especially to the enterococci. DBA, TBA, and BCA were mutagenic in the microsuspension assay, but the presence of the intestinal flora did not significantly alter the mutagenicity. BCA increased the activities of several enzymes, and therefore has the potential to affect the biotransformation of co-exposed compounds.
卤乙酸是饮用水消毒的副产物。该类中的几种化合物具有基因毒性，已被确定为啮齿动物肝癌致癌物。正常肠道细菌产生的酶可将一些前诱变剂和前致癌物转化为其生物活性形式。本研究旨在调查盲肠微生物群对卤乙酸致突变性的影响，并观察与接触卤乙酸相关的微生物群数量和酶活性的变化。将含有1mg/ml一氯乙酸（MCA）、一溴乙酸（MBA）、二氯乙酸（DCA）、二溴乙酸（DBA）、三氯乙酸（TCA）、三溴乙酸（TBA）或溴氯乙酸（BCA）的PYG培养基接种大鼠盲肠匀浆，并在37℃下厌氧培养。通过在选择性培养基上对微生物群数量进行计数来绘制生长曲线。在有无盲肠微生物群的情况下，孵育不同时间后，在沙门氏菌微悬液生物测定中测定致突变性。孵育15小时后，通过酶测定确定β-葡萄糖醛酸酶、β-半乳糖苷酶、β-葡萄糖苷酶、偶氮还原酶、硝基还原酶、脱氯酶和脱氯化氢酶的活性。除BCA外，卤乙酸对盲肠微生物群有毒，尤其是对肠球菌。DBA、TBA和BCA在微悬液测定中具有致突变性，但肠道菌群的存在并未显著改变其致突变性。BCA增加了几种酶的活性，因此有可能影响共同暴露化合物的生物转化。
