双硫仑生成的混合二硫化物可抑制苯并[a]芘诱导的诱变作用。

Mixed disulfides from disulfiram inhibit the benzo[a]pyrene induced mutagenesis.

作者信息

Lee B H, Lee S, Kim Y S, Bertram B, Wiessler M

机构信息

Institute of Environment and Life Science, Hallym University, Chunchon, South Korea.

出版信息

Mutat Res. 1996 Dec 20;371(3-4):215-20. doi: 10.1016/s0165-1218(96)90109-3.

DOI:10.1016/s0165-1218(96)90109-3

PMID:9008722

Abstract

Some mixed disulfides derived from disulfiram and endogenous thiol compounds have been synthesized, biochemically characterized and their potential antigenotoxic effects have been proposed. The present study evaluated the mutagenic and antimutagenic specificities of two mixed disulfides using S. typhimurium reversion assay, namely S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine (AC-DDTC) and-L-glutathione (GS-DDTC). The two mixed disulfides were not mutagenic to Salmonella strains TA98 and TA100 in the presence or absence of S9 mixture. The increased number of revertants by benzo[a]pyrene (B(a)P) has been reduced to the control level by the preincubation with AC-DDTC or GS-DDTC. It was not due to the killing effect of B(a)P, mixed disulfides or B(a)P-disulfide mixture. The antimutagenic effect of AC-DDTC was more potent than that of GS-DDTC. These results indicate that AC-DDTC and GS-DDTC may have a role to play in reducing the risk of mutagenic effects of B(a)P.

摘要

一些由双硫仑和内源性硫醇化合物衍生而来的混合二硫化物已被合成、进行了生化表征，并提出了它们潜在的抗基因毒性作用。本研究使用鼠伤寒沙门氏菌回复突变试验评估了两种混合二硫化物的诱变和抗诱变特异性，即S-（N，N-二乙基二硫代氨基甲酰基）-N-乙酰半胱氨酸（AC-DDTC）和-L-谷胱甘肽（GS-DDTC）。在有或没有S9混合物存在的情况下，这两种混合二硫化物对沙门氏菌菌株TA98和TA100均无诱变性。通过与AC-DDTC或GS-DDTC预孵育，苯并[a]芘（B(a)P）使回复突变体数量增加的情况已降至对照水平。这不是由于B(a)P、混合二硫化物或B(a)P-二硫化物混合物的杀伤作用。AC-DDTC的抗诱变作用比GS-DDTC更强。这些结果表明，AC-DDTC和GS-DDTC可能在降低B(a)P诱变作用风险方面发挥作用。