title: Polycyclic aromatic hydrocarbons and their quinones modulate the metabolic profile and induce DNA damage in human alveolar and bronchiolar cells.
abstract: The release of particulate pollutants into the air through burning of coal, crude oil, diesel, coal tar, etc. raises concerns of potential health hazards to the exposed human population. Polycyclic aromatic hydrocarbons (PAHs) are major toxic constituents of particulate matter (PM), which upon ingestion get metabolized to even more toxic metabolites such as quinones. The PAHs levels were assessed in both respirable particulate matter (RSPM, <10μM size) and suspended particulate matter (SPM, >10μM size) of urban ambient air (UAA) and that of major contributors viz. diesel exhaust particles (DEPs) and coal tar combustions emissions (CTCE). Seven US Environmental Protection Agency (USEPA) prioritized PAHs in RSPM and 10 in SPM were detected in UAA. Ten and 15 prioritized PAHs, respectively, were also detected in diesel exhaust particles (DEP) and coal tar combustion emission (CTCE) evidencing their release in the air. These PM associated PAHs for UAA, DEP and CTCE showed significant increase (p<0.05) in mutagenicity and mammalian genotoxicity in the order CTCE>DEP>UAA. Human lung alveolar (A549) and bronchiolar (BEAS-2B) cells when treated with PAH-metabolites viz. 1,4-benzoquinone (1,4-BQ), hydroquinone (HQ), 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ) and 9,10-phenanthroquinone (9,10-PQ) showed metabolic modulation in these cell lines with significant depletion of principal cellular metabolites viz. NADP, uracil, asparagines, glutamine, and histidine and accumulation of di-methyl amine and beta-hydroxybutyrate, identified using (1)H NMR spectroscopy. These results suggest that PAH-quinones induce genotoxic effects by modulating the metabolic machinery inside the cells by a combined effect of oxidative stress and energy depletion. Our data for metabolic profiling of human lung cells could also help in understanding the mechanism of toxicity of other xenobiotics.
authors.affiliation: Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Gurbani
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Bharti
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Godson R E E
authors.initials: GR
authors.lastname: Ana
authors.forename: Ambrish
authors.initials: A
authors.lastname: Verma
authors.forename: Altaf Husain
authors.initials: AH
authors.lastname: Khan
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Patel
authors.forename: M K R
authors.initials: MK
authors.lastname: Mudiam
authors.forename: Swatantra K
authors.initials: SK
authors.lastname: Jain
authors.forename: Raja
authors.initials: R
authors.lastname: Roy
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage; D004784:Environmental Monitoring; D006801:Humans; D007194:India; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology; D011809:Quinones / Q000032:analysis / Q000633:toxicity*; D012485:Salmonella typhi / Q000187:drug effects / Q000235:genetics
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D011809:Quinones
keywords: Genotoxicity; Human lung cells; Metabolic profiling; Polycyclic aromatic hydrocarbons (PAHs); Quinones