Mutagenicity of peroxyacetyl nitrate (PAN) in vivo: Tests for somatic mutations and chromosomal aberrations

Abstract

A series of experiments was conducted in which Chinese hamsters inhaled PAN, an ubiquitous pollutant that is present in the atmosphere at concentrations that are as high as, or higher than, other known genotoxic agents. The animals were exposed to PAN in air at concentrations of approximately 3 ppm for up to 1 month and then examined for somatic mutations and chromosomal aberrations. Mutations were assayed by measuring the frequency of thioguanine-resistant lung fibroblasts (isolated de novo and cultured). Chromosomal aberrations were assayed by measuring the frequency of micronuclei in either the bone marrow (polychromatic erythrocytes) or the lungs (binucleate lung fibroblasts cultured in the presence of cytochalasin B). The results for the test animals were compared to those from animals exposed similarly, but without PAN. Although in each experiment the mutation frequencies for the test animals were higher than the corresponding controls, the mutation frequencies were not significantly different from the concurrent negative controls (P > .05) or the historical controls, except for experiment C. In experiment C, there was a significant regression of mutation frequency versus dose (P < 0.001) if all of the historical controls for pooled animals are included at zero dose. No reproducible evidence of chromosomal breakage was found in either lung or bone marrow. Thus, although PAN has been found to be a bacterial mutagen, we did not find statistically significant evidence of mutagenicity in vivo. The toxicity of PAN limited the exposure concentration that could be used. When all of the PAN data were used, the best estimate of the mutagenic potency proved to be comparable to that of ethylene dibromide, a carcinogenic atmospheric pollutant.