Aryl and heterocyclic diazo compounds as potential environmental electrophiles.
4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003979:Diazonium Compounds / Q000009:adverse effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007042:Hypoxanthines / Q000494:pharmacology / Q000652:urine; D007093:Imidazoles / Q000378:metabolism; D009153:Mutagens; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D003979:Diazonium Compounds; D004785:Environmental Pollutants; D006571:Heterocyclic Compounds; D007042:Hypoxanthines; D007093:Imidazoles; D009153:Mutagens; D009573:Nitrites