Letter: In vitro detection of nitrosamines and other indirect alkylating agents by reaction with 3,4-dichlorothiophenol in the presence of rat liver microsomes.

A new method for the detection of indirect alkylating agents, such as the nitrosamines, using 3,4-dichlorothiophenol as t rapping agent in the presence of rat liver microsomes is reported. 3,4-Dichlorophenyl alkyl thioethers thus formed dur ing the incubation are detected by the use of a gas chromatography-mass spectrometry combinat ion unit and are quanti f ied by use of external standards. A series of methylalkylnitrosamines, used in the present experiments, predominant ly give rise to 3,4-dichlorophenyl methyl thioether, as compared with other alkyl thioethers. Branching in the (x posi t ion of the alkyl chain of the nitrosamines reduces the amount of the alkyl thioethers formed. Symmetrical dialkylni trosamines, when incubated as above, preferentially give rise to methyl thioether as compared with the corresponding alkyl thioethers. The results show a good relationship between carcinogenici ty and alkylating capacity of the nitrosamines. These f indings are also in agreement with the in vivo studies on alkylation of nucleic acids with different nitrosamines. This method can be used as a rapid screening technique for detection of indirect alkylating agents.