Prophage induction in lysogenic Escherichia coli with N-nitroso compounds and derivatives

Prophage induction in lysogenic Escherichia coli W1709 (iota) was determined for 29 N-nitroso compounds, 13 of their denitrosated derivatives, and 7 hydroxylamino and hydrazino analogues of nitrosamines. Minimal inducing concentrations of 0.1 to 2.0 mug/ml were demonstrated for eight nitrosamidines, and concentrations of 0.5 to 25.0 mug/ml were shown for six nitrosamides. Weak inducing activities were found with N,N-diethylhydroxylamine oxalate and N-methyl-N-phenylhydrazine sulfate, derivatives of inactive N-nitrosodiethylamine and N-nitrosomethylphenylamine, respectively. Inactive compounds including N-methyl-N-nitroso-p-toluenesulfonamide, 11 nitrosamines, 3 N, N'-dialkyl substituted-N-nitrosoureas, 13 denitrosated derivatives, and 5 hydroxylamino and hydrazino analogues of nitrosamines are listed. Since 7 of the 14 prophage-inducing nitrosamidines and nitrosamides reported thus far have carcinostatic activity in rodent tumor systems, it is concluded that the induction test may provide a useful screen for the detection of potential antitumor compounds. The induction test may also be useful for the detection of responsive N-nitroso compounds which may be potential toxicological hazards in the environment since, of the six active nitrosamides, five have already been reported to produce mutagenic and carcinogenic effects, four produce chromosomedamaging effects, and two produce teratogenic effects. Use of the prophage induction system for detection of biologically active intermediates formed by N-nitroso compounds under physiological conditions is considered.