Review of the genotoxicity of nitrogen oxides.

Nitrogen oxides (NOx) are formed in combustion processes and are major pollutants in urban air. Relatively few studies on the genotoxicity of NO2 and NO have been performed. These studies indicate that NO2 is genotoxic in vitro, but the effect of NO seems to be very slight. One in vivo study showed chromosome aberrations and mutations in lung cells after inhalation of NO2 (and NO), but tests for chromosome aberrations in lymphocytes and spermatocytes or micronuclei in bone marrow were negative after inhalation of NO2. Based on present studies, there is no clear evidence of a carcinogenic potential of NO2, although lung adenomas were induced in the susceptible strain A/J mouse. The primary metabolites of NOx are nitrite and nitrate. Nitrate seems to be devoid of genotoxic properties, but nitrite is genotoxic in vitro, and there are also positive in vivo results. Cancer studies have been mainly negative. However, carcinogenic nitrosamines have been shown to be formed in vivo after inhalation of NO2. Nitrogen oxides are key components in atmospheric smog formation, which may lead to secondary effects. Strongly mutagenic nitro-PAH compounds are easily formed, and mutagenic reaction products may be formed photochemically from alkenes.