Krewet E, Müller G, Norpoth K
Institute of Hygiene and Occupational Medicine, University of Essen, F.R.G.
Toxicology. 1989 Nov;59(1):67-79. doi: 10.1016/0300-483x(89)90157-1.
Chlorobenzene (CB) was administered to male Wistar rats. Twenty-four-hour urine samples were collected over a period of 7 days. p-Chlorophenylmercapturic acid, chlorophenols and a guanine adduct were determined by chromatographic methods. The excretion pattern of p-chlorophenyl-mercapturic acid did not seem to be significantly affected by phenobarbital. To analyze for the chlorophenols and guanine adducts, diluted urine was subjected to cation exchange chromatography using UV-detection. Fractions were found containing chlorophenols and a compound showing chromatographic properties similar to those of the synthetic N7-phenylguanine. The results of the HPLC analyses suggested the presence of a guanine adduct excreted on days 1 and 2 and between days 4 and 6 post-administration. There were no compounds detected which were identical with p-, m- or o-isomers of N7-chlorophenylguanine. The excretion of p- and m-chlorophenols by phenobarbital-pretreated animals was twice as high as that in untreated rats. A 4-fold increase was detected for o-chlorophenol. It is assumed that it is mainly direct hydroxylation that can be induced by phenobarbital. Dehalogenated phenolic metabolites may be capable of covalent binding to DNA.
将氯苯（CB）给予雄性Wistar大鼠。在7天的时间内收集24小时尿液样本。采用色谱法测定对氯苯基巯基尿酸、氯酚和一种鸟嘌呤加合物。苯巴比妥似乎对尿中对氯苯基巯基尿酸的排泄模式没有显著影响。为了分析氯酚和鸟嘌呤加合物，对稀释后的尿液进行阳离子交换色谱分析，并采用紫外检测。发现部分馏分含有氯酚和一种具有与合成N7 - 苯基鸟嘌呤相似色谱特性的化合物。高效液相色谱分析结果表明，在给药后第1天和第2天以及第4天至第6天之间存在一种排泄的鸟嘌呤加合物。未检测到与N7 - 氯苯基鸟嘌呤的对、间或邻异构体相同的化合物。经苯巴比妥预处理的动物，其对氯酚和间氯酚的排泄量是未处理大鼠的两倍。邻氯酚的排泄量增加了4倍。据推测，这主要是由苯巴比妥诱导的直接羟基化作用。脱卤代酚类代谢产物可能能够与DNA发生共价结合。
