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Molecular Compositions, Mutagenicity, and Mutation Spectra of Atmospheric Oxidation Products of Alkenes and Dienes Initiated by NOx + UV or Ozone: A Structure-Activity Analysis
Citation:
Lewandowski, M., T. Riedel, J. Krug, T. Kleindienst, M. Meier, A. Long, S. Warren, AND D. DeMarini. Molecular Compositions, Mutagenicity, and Mutation Spectra of Atmospheric Oxidation Products of Alkenes and Dienes Initiated by NOx + UV or Ozone: A Structure-Activity Analysis. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 58(12):18846−18855, (2024). https://doi.org/10.1021/acs.est.4c04603
Impact/Purpose:
Decades of studies have identified the sources of VOCs (both anthropogenic and biogenic), the toxicology of many VOCs, and the complex chemical reactions involving the interaction of VOCs with sunlight, resulting in an array of photoproducts. However, much remains to be learned regarding the relationship between the structures of VOCs and the molecular composition and mutagenic potencies of the atmospheres containing their photooxidation products, which are the primary toxicants resulting from VOC-associated air pollution. Our current study is aimed at identifying the structures of VOCs whose photooxidation produce the most mutagenic atmospheres, identifying the classes of mutations induced by these atmospheres, and examining how those mutations might relate to non-smoker-associated lung cancer, which is likely due to air pollution. Recently, we found that despite the structural similarities between isoprene and 2-pentene, the atmosphere resulting from the photooxidation of isoprene was 8 times more mutagenic than that from 2-pentene, suggesting that the number and/or location of C=C bonds and methyl side groups influence the formation of mutagenic products from the photooxidation of alkene precursors (Krug et al., submitted to Atmos Environ). Here we have extended these observations by evaluating nine additional alkene or diene VOCs that are structurally related to either isoprene or 2-pentene to assess the influence of branching and C=C bond count and location on the photochemical formation of mutagenic gas-phase products. We conducted statistical correlations between the concentration of the identified molecular compositions, mutagenic potencies, and mutation spectra to infer oxidation pathways most relevant to mutagen formation. Finally, we examined the association of the classes of mutations induced by these atmospheres with those found in non-smoking-associated lung cancer, which is potentially due to exposure to gas-phase air pollution. We found that the mutagenic potency of atmospheres produced by photooxidation of VOCs without a C=C bond is zero, is higher for those with two rather than with one C=C bond, and the highest for those with two external C=C bonds. Based on CIMS chemistry, we found high correlations between the molecular compositions (especially for nitrogen-containing molecules) of the atmospheres, the mutagenic potencies of the atmospheres, and the induction by the atmospheres of C to T mutations. DNA sequence analysis of the Salmonella mutants showed that these atmospheres induced primarily two classes of mutations (C to T and C to A) that are also the two main classes found in non-smoker lung tumors, which are likely due to air pollution. These results suggest that VOC control strategies that focus on dienes rather than alkanes or even alkenes with a single C=C bond, will be most effective in reducing VOC-associated air pollution and its potential health effects. Studies such as these are essential to understanding the impact of VOC photooxidation products on public health and environmental pollution. Current control strategies do not consider the toxicology of these photooxidation products, and our studies show that examining the toxicology of just the parent VOC fails to identify those VOCs that are the most important contributors to potential health effects from VOC-associated air pollution.
Description:
Photooxidation products resulting from volatile organic compounds (VOCs) reacting with sunlight are important contributors to gas-phase air pollution. We characterized the product-weighted mutagenic potencies (rev m3 mgC-1 h-1) in Salmonella TA100 of atmospheres resulting from the hydroxyl radical (OH)-initiated photochemical oxidation of 11 C4 or C5 alkenes or dienes in the presence of nitric oxide (NO) and from the ozonolysis of four VOCs without NO (isoprene; 1,3-pentadiene; 1,4-pentadiene; and 1,3-butadiene). Irradiated atmospheres from precursors with a single C¿C bond (3-methyl-1-butene, 2-methyl-1-butene, cis/trans-2-pentene, 2-methyl-2-butene, 1-butene, and 1-pentene) had low potencies (<5), whereas linear dienes with terminal C¿C bonds had high potencies (50-65). Dienes with a branched structure (isoprene) or internal C¿C bonds (1,3-pentadiene) had intermediate potencies (15-20). No VOCs were mutagenic without photochemical oxidation. VOCs+O3 in the dark produced less mutagenic atmospheres than photochemistry in the presence of NO. Atmospheres induced primarily C to T and C to A mutations, the main base substitutions in nonsmoker lung cancer. Atmospheres from the photooxidation of isoprene and 1,3-pentadiene also induced GG to TT, the signature mutation of peroxyacetyl nitrate. Five molecular compositions identified by Chemical Ionization Mass Spectrometry (CIMS), most containing nitrogen, correlated (r = 0.76-0.85) with the mutagenic potencies of irradiated atmospheres; most had a likely nitrate functional group. Assessment of the mutagenicity of emitted VOCs should consider VOC photooxidation products, especially dienes with terminal C¿C bonds, as these products likely contribute to overall health effects from ambient air pollution.
URLs/Downloads:
DOI: Molecular Compositions, Mutagenicity, and Mutation Spectra of Atmospheric Oxidation Products of Alkenes and Dienes Initiated by NOx + UV or Ozone: A Structure-Activity Analysis
https://pubmed.ncbi.nlm.nih.gov/39374177/