二乙基二硫代氨基甲酸盐对二甲基亚硝胺诱导的肝脏DNA链断裂和肝细胞坏死的抑制作用。

Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate.

作者信息

Abanobi S E, Popp J A, Chang S K, Harrington G W, Lotlikar P D, Hadjiolov D, Levitt M, Rajalakshmi S, Sarma D S

出版信息

J Natl Cancer Inst. 1977 Feb;58(2):263-71. doi: 10.1093/jnci/58.2.263.

DOI:10.1093/jnci/58.2.263

Abstract

Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1, N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxy-methanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects.

摘要

二乙基二硫代氨基甲酸盐（DEDTC）可预防雄性Wistar大鼠中由二甲基亚硝胺（DMN）诱导的肝脏DNA链断裂和肝细胞坏死。相比之下，DEDTC并不抑制由其他几种化学致癌物（N-羟基-2-乙酰氨基芴、3-羟基黄嘌呤、黄曲霉毒素B1、N-乙酰氧基-2-乙酰氨基芴、甲磺酸甲酯、甲基亚硝基脲和乙酸甲基偶氮甲醇）引起的肝脏DNA片段化，无论它们是否需要代谢激活。氨基乙腈发挥了与DEDTC类似的作用。这种抑制作用是短暂的，至少持续4小时，而要获得超过4小时的保护则需要多次给予DEDTC。DEDTC还抑制了DMN的血清清除率、肝脏DNA的甲基化以及在由雄性Wistar大鼠或仓鼠制备的体外肝微粒体系统中DMN的氧化去甲基化。DMN代谢的干扰似乎是DEDTC阻止DMN诱导的生化和生物学效应的机制。