title: Effects of co-exposure of benzene, toluene and xylene to Drosophila melanogaster: alteration in hsp70, hsp60, hsp83, hsp26, ROS generation and oxidative stress markers.
abstract: Benzene, toluene and xylene are monocyclic aromatic hydrocarbon compounds, used both as individual compound and as mixtures, in industry as well as household. Previous studies involving exposures to these compounds, individually, have shown that benzene was more toxic compared to toluene or xylene. Here, we tested a working hypothesis that toluene and/or xylene in a mixture containing benzene affect benzene induced toxicity in a non-target organism, Drosophila melanogaster. We exposed D. melanogaster larvae transgenic for hsp70, hsp83 or hsp26 and wild type (Oregon R strain) larvae to 25.0-100.0mM benzene, 25.0-100.0mM toluene and 25.0-100mM xylene, individually or in mixtures. Subsequently, we examined the expression of stress genes (encoding heat shock proteins, hsps), generation of reactive oxygen species (ROS), induction of anti-oxidant stress markers and emergence of flies under treatment as well as control conditions. We observed that all these endpoints were significantly altered in all the treatment groups compared to their respective controls. However, the magnitude of toxicity of a benzene-toluene (BT) or benzene-xylene (BX) or benzene-toluene-xylene (BTX) mixture was significantly lower in the organism than that of individual chemical. Our results also show the modulation of toluene toxicity by xylene. Present study suggests antagonistic effect of xylene and toluene on benzene toxicity and additive/synergistic effect of xylene on toluene induced toxicity. Thus, expression of stress genes may be used as an assay for detection of early cellular toxicity. Further, our study supports the use of Drosophila as an alternative animal model for first tier screening of adverse effects of chemical mixtures.
authors.affiliation: Embryotoxicology Section, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh, India; Council of Scientific and Industrial Research, New Delhi, India.
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Ram
authors.forename: M
authors.initials: M
authors.lastname: Mishra
authors.forename: M
authors.initials: M
authors.lastname: Shrivastava
authors.forename: D K
authors.initials: DK
authors.lastname: Saxena
authors.forename: D Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014050:Toluene / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014992:Xylenes / Q000633:toxicity
chemical_list: D015415:Biomarkers; D018834:Chaperonin 60; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C087442:Hsp26 protein, Drosophila; C089272:Hsp83 protein, Drosophila; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D014992:Xylenes; D014050:Toluene; D001554:Benzene