Specific reduction of N,N-dimethylnitrosamine mutagenicity in Drosophila melanogaster by dimethyl sulfoxide.
Dimethyl sulfoxide (DMSO) used as a solvent has been observed to complicate mutagenicity screens by interacting with tested chemicals to yield false positives or negatives. We have used DMSO as a solvent in the Drosophila melanogaster recessive sex-linked lethal mutation assay and find that it reduces, but does not abolish, the detectable mutagenicity of N,N-dimethylnitrosamine (DMN). Its use as a solvent with procarbazine, another promutagen, shows no effect on mutagenicity in Drosophila. DMSO does not exhibit a general inhibitory action on microsome activity when ecdysone 20-monooxygenase activity is used as a measure of cytochrome P-450 activity. We were unable to detect the low DMN demethylase activity in the strain used. Hence, the inhibitory effect of DMSO in Drosophila at both the physiological and biological level appears to be limited and not general in action. Because DMN and DMSO are similar in structure, it is possible that DMSO is interacting with a DMN demethylase in Drosophila. This might lead to a reduction in the conversion of DMN to a mutagen. Consequently, from the results of this study and others DMSO should be used cautiously as a solvent in Drosophila mutagen screening.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D005188:False Negative Reactions; D005804:Genes, Lethal; D005808:Genes, Recessive; D009152:Mutagenicity Tests / Q000379:methods*; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis; D012997:Solvents / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000032:analysis
D012997:Solvents; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C020095:ecdysone 20-hydroxylase; D010089:Oxidoreductases, N-Demethylating; D004128:Dimethylnitrosamine; D004121:Dimethyl Sulfoxide