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暴露于二氯甲烷的小鼠和大鼠肝脏中缺乏尿苷二磷酸葡萄糖醛酸基转移酶(UDS)活性。

Lack of UDS activity in the livers of mice and rats exposed to dichloromethane.

作者信息

Trueman R W, Ashby J

机构信息

Imperial Chemical Industries Plc, Central Toxicology Laboratory, Macclesfield, Cheshire, England.

出版信息

Environ Mol Mutagen. 1987;10(2):189-95. doi: 10.1002/em.2850100209.

DOI:10.1002/em.2850100209
PMID:3691491
Abstract

Dichloromethane (DCM) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male mice and rats in vivo. Two types of experiment were conducted. In the first, Alpk:AP rats were exposed by oral gavage to 100, 500, or 1,000 mg/kg DCM and hepatocytes assessed for UDS via autoradiography 4 and 12 hours later. In the second, Fischer F344 rats or B6C3F1 mice were exposed by inhalation to either 2,000 or 4,000 ppm of DCM for either 2 or 6 hours, and hepatocytes assessed for UDS immediately after exposure. The dose levels and strains of rodent employed in the latter protocol correspond to those employed in a recent cancer bioassay of DCM conducted by the U.S. National Toxicology Program. DCM failed to induce UDS in any of the experiments. These data are discussed within the context of other evidence indicating DCM to be nongenotoxic in vivo, despite its reported carcinogenicity in the mouse.

摘要

已对二氯甲烷(DCM)在雄性小鼠和大鼠肝脏中引发非预定DNA合成(UDS)的能力进行了体内评估。进行了两种类型的实验。在第一个实验中,通过灌胃给Alpk:AP大鼠施用100、500或1000 mg/kg的DCM,并在4小时和12小时后通过放射自显影术评估肝细胞的UDS。在第二个实验中,将Fischer F344大鼠或B6C3F1小鼠吸入2000或4000 ppm的DCM,持续2或6小时,并在接触后立即评估肝细胞的UDS。后一实验方案中使用的啮齿动物剂量水平和品系与美国国家毒理学计划最近进行的DCM癌症生物测定中使用的一致。在任何实验中,DCM均未诱导UDS。尽管有报道称DCM在小鼠中具有致癌性,但结合其他表明其在体内无遗传毒性的证据对这些数据进行了讨论。

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