title: Genotoxicity of hydroquinone in A549 cells.
abstract: Hydroquinone (HQ) is found in natural and anthropogenic sources including food, cosmetics, cigarette smoke, and industrial products. In addition to ingestion and dermal absorption, human exposure to HQ may also occur by inhaling cigarette smoke or polluted air. The adverse effects of HQ on respiratory systems have been studied, but genotoxicity HQ on human lung cells is unclear. The aim of this study was to investigate the cytotoxicity and genotoxicity of HQ in human lung alveolar epithelial cells (A549). We found that HQ induced a dose response in cell growth inhibition and DNA damage which was associated with an increase in oxidative stress. Cytotoxicity results demonstrated that HQ was most toxic after 24 h (LC50 = 33 μM) and less toxic after 1 h exposure (LC50 = 59 μM). Genotoxicity of HQ was measured using the Comet assay, H2AX phosphorylation, and chromosome aberration formation. Results from the comet assay revealed that DNA damage was highest during the earlier hours of exposure (1 and 6 h) and thereafter was reduced. A similar pattern was observed for H2AX phosphorylation suggesting that damage DNA may be repaired in later exposure hours. An increase in chromosomal aberration corresponded with maximal DNA damage which further confirmed the genotoxic effects of HQ. To investigate whether oxidative stress was involved in the cytotoxic and genotoxic effects of HQ, cellular glutathione and 8-Oxo-deoguanisone (8-Oxo-dG) formation were measured. A decrease in the reduced glutathione (GSH) and an increase oxidized glutathione (GSSG) was observed during the early hours of exposure which corresponded with elevated 8-Oxo-dG adducts. Together these results demonstrate that HQ exerts its cytotoxic and genotoxic effects in A549 lung cells, probably through DNA damage via oxidative stress.
authors.affiliation: National Research Centre for Environmental Toxicology-Entox, The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, 4108, Australia.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Dionne
authors.initials: D
authors.lastname: Arthur
authors.forename: Faye
authors.initials: F
authors.lastname: Liu
authors.forename: Jongwha
authors.initials: J
authors.lastname: Lee
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.forename: Jack C
authors.initials: JC
authors.lastname: Ng
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000139:chemically induced; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects*; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; C468783:H2AX protein, human; D006657:Histones; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; C031927:hydroquinone