Formation of a highly mutagenic diazo compound from the bamethan-nitrite reaction.
A variety of cardiovascular drugs were treated with 10 equivalent amounts of nitrite in acidic solutions. Among 18 drugs, a preparation of bamethan [1-(4-hydroxyphenyl)-1-hydroxy-2-butylaminoethane] showed strikingly high mutagenicity by this treatment toward Salmonella typhimurium TA98 and TA100 strains. Treatment of bamethan with an equivalent amount of nitrite gave N-nitrosobamethan I which was not mutagenic. However, treatment of bamethan with 4 equivalent amounts of nitrite afforded a highly mutagenic compound II, which was identified as 3-diazo-N-nitrosobamethan by its physicochemical analysis and chemical properties. Specific mutagenic activity of II was 9200 His+ revertants/mu mole toward TA98 and 8060 His+ revertants/mu mole toward TA100. Addition of microsomal system little affected the activity. Bamethan is administrated orally during long period for treatment of cardiovascular diseases. It is noted that this drug can produce the highly mutagenic diazo compound by reaction with nitrite which is present in digestive tracts.
D000818:Animals; D002317:Cardiovascular Agents / Q000378:metabolism; D004983:Ethanolamines / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009573:Nitrites / Q000378:metabolism*; D010627:Phenethylamines; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*
D002317:Cardiovascular Agents; D004983:Ethanolamines; D009573:Nitrites; D010627:Phenethylamines; C051613:3-diazo-N-nitrosobamethan