Genotoxic activities of drug-nitrite interaction products.

At first 28 orally administered drugs, considered to be potentially nitrosatable on the basis of their chemical structure, have been nitrosated with nitrite under simulated stomach conditions. A maximum daily dose of each drug was incubated with a nitrite concentration that can be found after a normal meal in the stomach at 37 degrees C over 1 h. Reaction was started at pH 6.8-7.0 and stopped at pH 2.0, so we had the same pH change that occurs in the stomach. Secondly the genotoxic activities of drug-nitrite interaction products were tested by the umu-test with Salmonella typhimurium TA 1535/pSK1002 as tester strain in the presence and absence of metabolic activation. By the umu-test, among the nitrosation products of drugs examined 22 products showed genotoxicity at different levels. Other six products showed negative results by the umu-test.