Elliott B M, Ashby J
Imperial Chemical Industries Limited, Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Carcinogenesis. 1980;1(12):1049-57. doi: 10.1093/carcin/1.12.1049.
Two possible mechanisms for the reported carcinogenic synergism between ethylene dibromide (EDB) and disulfiram have been investigated in vivo and in vitro, the first involving increased production of an EDB-derived glutathione mustard and the second increased production of bromoacetaldehyde. Consistent with both of these suggested mechanisms, repeated administrations of disulfiram to rats inreased liver glutathione-S-transferase activity and decreased liver low Km aldehyde dehydrogenase activity. However, when added to a rat liver S-9 fraction in vitro, disulfiram decreased transferase activity and only depressed the dehydrogenase activity after a period of preincubation. Although the mutagenic potency of EDB to Salmonella typhimurium was slightly enhanced in vitro by the addition of a rat liver S-9 fraction, the further addition of disulfiram to the assay medium produced no additional change. Similarly, the addition of a range of S-9 and S-0.5 liver fractions derived from disulfiram-treated rats also failed to enhance significantly its mutagenic potency over the normal S-9 fraction. The general implications of these findings are discussed.
已在体内和体外研究了二溴乙烷（EDB）与双硫仑之间所报道的致癌协同作用的两种可能机制，第一种机制涉及二溴乙烷衍生的谷胱甘肽氮芥产量增加，第二种机制涉及溴乙醛产量增加。与这两种推测机制均相符的是，对大鼠反复给予双硫仑会提高肝脏谷胱甘肽-S-转移酶活性，并降低肝脏低Km醛脱氢酶活性。然而，在体外将双硫仑添加到大鼠肝脏S-9组分中时，双硫仑会降低转移酶活性，并且仅在预孵育一段时间后才会抑制脱氢酶活性。尽管通过添加大鼠肝脏S-9组分在体外略微增强了二溴乙烷对鼠伤寒沙门氏菌的致突变能力，但向测定培养基中进一步添加双硫仑并未产生额外变化。同样，添加一系列来自双硫仑处理大鼠的S-9和S-0.5肝脏组分，也未能使其致突变能力比正常S-9组分显著增强。讨论了这些发现的一般意义。
