title: Synergistic increase in cell lethality by dieldrin and H2O2 in rat thymocytes: effect of dieldrin on the cells exposed to oxidative stress.
abstract: Dieldrin, one of persistent pesticides, is highly resistant to biotic and abiotic degradation. It is accumulated in organisms. Recent studies suggest that dieldrin exerts a potent cytotoxic action on cells exposed to oxidative stress. In this study, the effect of dieldrin on rat thymocytes exposed to hydrogen peroxide (H2O2)-induced oxidative stress was examined. Dieldrin at 5μM and H2O2 at 300μM slightly increased cell lethality from a control value of 5.4±0.5% (mean±standard deviation of four experiments) to 7.8±1.3% and 9.0±0.3%, respectively. Simultaneous application of dieldrin and H2O2 significantly increased cell lethality to 46.2±1.8%. The synergistic increase in cell lethality was dependent on dieldrin concentration (0.3-5μM) but not on H2O2 concentration (30-300μM). Dieldrin accelerated H2O2-induced cell death, which was estimated with the help of annexin V-FITC and propidium iodide. Presence of either dieldrin or H2O2 decreased the cellular content of nonprotein thiol and increased intracellular Zn(2+) concentration. The combination of dieldrin and H2O2 further pronounced these effects. TPEN, a chelator of intracellular Zn(2+), significantly attenuated the synergistic increase in cell lethality induced by dieldrin and H2O2. It is, therefore, suggested that dieldrin augments the cytotoxicity of H2O2 in a Zn(2+)-dependent manner.
authors.affiliation: Division of Environmental Symbiosis Studies, Graduate School of Integrated Arts and Sciences, University of Tokushima, Tokushima 770-8502, Japan.
authors.forename: Tsolmon
authors.initials: T
authors.lastname: Chimeddorj
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakane
authors.forename: Miyuki
authors.initials: M
authors.lastname: Inai
authors.forename: Masaya
authors.initials: M
authors.lastname: Satoh
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Oyama
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D004026:Dieldrin / Q000633:toxicity*; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000633:toxicity*; D005029:Ethylenediamines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D004785:Environmental Pollutants; D005029:Ethylenediamines; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D004026:Dieldrin; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
keywords: Cytotoxicity; Dieldrin; Hydrogen peroxide; Intracellular Zn(2+); Nonprotein thiol; Oxidative stress