Genotoxic effects of PM10 and PM2.5 bound metals: metal bioaccessibility, free radical generation, and role of iron

Abstract

The present study was undertaken to examine the possible genotoxicity of ambient particulate matter (PM₁₀ and PM_2.5) in Pune city. In both size fractions of PM, Fe was found to be the dominant metal by concentration, contributing 22% and 30% to the total mass of metals in PM₁₀ and PM_2.5, respectively. The speciation of soluble Fe in PM₁₀ and PM_2.5 was investigated. The average fraction of Fe³⁺ and Fe²⁺ concentrations in PM_2.5 was 80.6% and 19.3%, respectively, while in PM_2.5 this fraction was 71.1% and 29.9%, respectively. The dominance of Fe(III) state in both PM fractions facilitates the generation of hydroxyl radicals (^·OH), which can damage deoxyribose nucleic acid (DNA), as was evident from the gel electrophoresis study. The DNA damage by ^·OH was supported through the in silico density functional theory (DFT) method. DFT results showed that C8 site of guanine (G)/adenine (A) and C6 site of thymine (T)/cytosine (C) would be energetically more favorable for the attack of hydroxyl radicals, when compared with the C4 and C5 sites. The non-standard Watson-Crick base pairing models of oxidative products of G, A, T and C yield lower-energy conformations than canonical dA:dT and dG:dC base pairing. This study may pave the way to understand the structural consequences of base-mediated oxidative lesions in DNA and its role in human diseases.

Keywords: Bioaccessibility of metals; DNA damage; Fe speciation; Free radicals; In silico DFT study.