Assessment of Fine Particulate Matter (PM2.5) Induced Cyto-Genotoxicity in a Highly Polluted Urban Environment: Evidence from Lahore, Pakistan
摘要
Lahore’s air quality has remained worst globally since 2022, with the air quality index (AQI) exceeding an unprecedented level of 1,587, far beyond the recommended threshold (300) as established by United States Environmental Protection Agency (U.S. EPA). According to the world health organization (WHO) safety guidelines, the permissible 24-h Particulate Matter (PM2.5) concentration is 15 µgm-3. However, the present study, conducted at Institute of Biochemistry and Biotechnology (IBBt), University of Veterinary and Animal Sciences (UVAS), Lahore (31° 52′ N, 74°35′ E) recorded the average daily PM2.5 concentrations of 350 to 400 µgm-3. Inverse distance weighting (IDW) of PM2.5 monitoring data revealed excess PM2.5 burden in central and north-central urban regions of Lahore with negligible levels in the rural areas. For MTT assay, human lymphocytes were exposed to various dose concentrations of PM2.5, ranging from 50–500 µg/mL and EC50 was observed at 125 µg/mL. Additionally, EC50/2 and 3xEC50/2 values were recorded at 250 µg/mL and 500 µg/mL respectively. The alkaline comet assay revealed a significant increase in DNA damage, shown by elevated damage index and fragmentation percentage (P ≤ 0.05). An increased formation of micronuclei, binuclei and nuclear buds was observed by micronucleus assay. The lower level of cytokinesis block proliferation index (CBPI), along with elevated percent (%) cytostasis, indicated a marked suppression in the proliferation of lymphocytes (P ≤ 0.05). Importantly, all these cyto-genotoxic effects were dose-dependent with the highest damage observed at 500 µg/mL and the lowest at 125 µg/mL upon comparison to the control groups. Furthermore, unregulated expression rates of OGG1 and HPRT1 were attenuated at 500 µg/mL PM2.5 dose, reflective of the failure of DNA repair at such extreme levels. This study highlights the need for urgent policy-based interventions to secure public health and mitigate the long-term adverse health consequences of chronic air pollution exposure.