Possible formation of nitrosamine in guinea pigs following exposure to nitrogen dioxide and dimethylamine.

Abstract

The possibility of formation of nitrosamine was investigated in animals exposed to a combination of dimethylamine (DMA) and NO2. First, the distribution and covalent binding of DMA and dimethylnitrosamine (DMN) in rats and guinea pigs were determined. The apparent volume of distribution and biological half-life for [14C]-DMA or [14C]DMN did not reveal any species difference. In general, there were no marked differences in accumulation of radioactivity in tissues of guinea pigs and rats 4 h after the administration of DMA, while the guinea pig tissues showed higher accumulation after DMN administration. Nucleic acid fractions prepared from liver and lungs of both species following administration of DMN or DMA in vivo showed much higher covalent binding with DMN than with DMA. Furthermore, the covalent binding of DMN was found to be due to bioactivation, whereas the DMA binding was nonspecific. Since guinea pig liver showed a higher degree of covalent binding than rat liver, this species was used to investigate the possible increase in covalent binding in the presence of NO2 and DMA as a reflection of DMN formation. There was no evidence of enhancement of covalent binding when animals pretreated with [14C]-DMA were exposed for various lengths of time to different concentrations of NO2.