Pool B L, Bertram B, Wiessler M
Carcinogenesis. 1982;3(5):563-7. doi: 10.1093/carcin/3.5.563.
Disulfiram (DSF) can considerably alter the organotropy of chemical carcinogens. For N-nitrosodimethylamine and for N-nitrosodiethylamine the organotropy is shifted from the liver to the nasal cavity or the oesophagus, respectively. Whereas the influence of DSF or its metabolites on enzyme systems has been studied, little is known about its interaction with the carcinogens at a molecular level. Therefore, postulated reaction products of a series of alpha-hydroxylated N-nitroso-dialkylamines and dithiocarbamate were synthesized and tested for mutagenicity in Salmonella typhimurium TA 1535. The results show that the compounds conjugated at a primary alpha-C-atom are not mutagenic, whereas those conjugated at a secondary alpha-C-atom are active. The primary N-nitroso-dithiocarbamates represent unique examples of inactivated dialkyl-nitrosamine derivatives. In addition, their formation in vitro was indirectly demonstrated. The possible role these inactivated compounds may play during the DSF-modulation of carcinogenesis will be discussed.
双硫仑（DSF）可显著改变化学致癌物的器官亲和性。对于N-亚硝基二甲胺和N-亚硝基二乙胺，其器官亲和性分别从肝脏转移至鼻腔或食管。尽管已对DSF或其代谢产物对酶系统的影响进行了研究，但对其在分子水平上与致癌物的相互作用却知之甚少。因此，合成了一系列α-羟基化N-亚硝基二烷基胺与二硫代氨基甲酸盐的假定反应产物，并在鼠伤寒沙门氏菌TA 1535中测试其致突变性。结果表明，在伯α-碳原子处共轭的化合物无致突变性，而在仲α-碳原子处共轭的化合物具有活性。伯N-亚硝基二硫代氨基甲酸盐是失活二烷基亚硝胺衍生物的独特实例。此外，间接证明了它们在体外的形成。将讨论这些失活化合物在DSF调节致癌过程中可能发挥的作用。
