Genotoxic activities of drug-nitrite interaction products

Ozhan G., Alpertunga B.

DRUG AND CHEMICAL TOXICOLOGY, vol.26, no.4, pp.295-308, 2003 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 4
  • Publication Date: 2003
  • Doi Number: 10.1081/dct-120024844
  • Journal Name: DRUG AND CHEMICAL TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.295-308
  • Keywords: drug-nitrite interaction, Umu-test, N-nitrosamines, genotoxicity, N-NITROSO COMPOUNDS, AMES TEST, MUTAGENICITY, TESTS, NITROSOCIMETIDINE, CHLORDIAZEPOXIDE, DNA
  • Istanbul University Affiliated: Yes

Abstract

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 37degreesC 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.