Mori M, Matsuhashi T, Miyahara T, Shibata S, Izima C, Kozuka H
Toxicol Appl Pharmacol. 1984 Oct;76(1):105-12. doi: 10.1016/0041-008x(84)90033-4.
2,4-Dinitrotoluene (2,4-DNT) is an important industrial nitroaromatic compound. 2,4-Diaminotoluene (2,4-DAT), one of the urinary metabolites of 2,4-DNT, is carcinogenic when fed to rats. The objectives of these studies were to determine whether 2,4-DAT was formed from 2,4-DNT in rat liver and to clarify the nature of enzymes responsible for reduction of 2,4-DNT to 2,4-DAT. Data obtained from thin-layer and high-pressure liquid chromatography indicated that metabolites produced by microsomal preparations were 2-amino-4-nitrotoluene (2A4NT) and its isomer (4A2NT). This microsomal activity is probably mediated by cytochrome P-450 because the reduction is blocked by carbon monoxide and primary amines [aniline, n-octylamine, and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA)]. In contrast, 2,4-DNT was metabolized via 2A4NT and 4A2NT to 2,4-DAT by cytosolic preparations. The greatest part of the reduction activity was due to cytosolic xanthine oxidase because the reduction was blocked by allopurinol. The results of this investigation suggest that reduction of 2,4-DNT to 2,4-DAT by cytosolic xanthine oxidase may play a role in 2,4-DNT hepatocarcinogenicity.
2,4-二硝基甲苯（2,4-DNT）是一种重要的工业硝基芳香化合物。2,4-二氨基甲苯（2,4-DAT）是2,4-DNT的尿代谢产物之一，给大鼠喂食时具有致癌性。这些研究的目的是确定大鼠肝脏中2,4-DAT是否由2,4-DNT形成，并阐明负责将2,4-DNT还原为2,4-DAT的酶的性质。从薄层色谱和高压液相色谱获得的数据表明，微粒体制剂产生的代谢产物是2-氨基-4-硝基甲苯（2A4NT）及其异构体（4A2NT）。这种微粒体活性可能由细胞色素P-450介导，因为一氧化碳和伯胺[苯胺、正辛胺和2,4-二氯-6-苯氧基乙胺（DPEA）]会阻断这种还原反应。相比之下，2,4-DNT通过2A4NT和4A2NT被细胞溶质制剂代谢为2,4-DAT。还原活性的最大部分归因于细胞溶质黄嘌呤氧化酶，因为别嘌呤醇会阻断这种还原反应。这项研究的结果表明，细胞溶质黄嘌呤氧化酶将2,4-DNT还原为2,4-DAT可能在2,4-DNT的肝脏致癌性中起作用。
