The induction/loss of the oxidant-resistant phenotype of Chinese hamster ovary (CHO) cell variants does not correlate with sensitivity to DNA single strand breakage by hydrogen peroxide.
Hydrogen peroxide resistant variants of Chinese hamster ovary (CHO) cells characterized by different levels of resistance to growth inhibition induced by the oxidant displayed a decreased susceptibility to the induction of DNA single strand breakage by hydrogen peroxide. Resistance to DNA damage, however, was maximal in cells resistant to killing by low concentrations of H2O, and did not increase further in cells characterized by a much higher resistance to the toxic action of the oxidant. Different sensitivities to the induction of DNA single strand breakage observed in wild type and resistant sublines were related to a decreased susceptibility/differential depletion of H2O2, rather than being dependent on different velocities in DNA repair processes. Growth of resistant cells in the absence of H2O2 resulted in a rapid loss of resistance to induction of DNA strand scission by H2O2. Cells retained resistance to the growth-inhibitory effect of the oxidant under conditions where resistance to the production of DNA single strand breaks was lost. Experiments aimed at elucidating the molecular basis for resistance to DNA damage induction by H2O2 have demonstrated that this effect is dependent upon the catalase activity of the specific sublines as well as on their different total protein content.
Sestili
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Istituto di Farmacologia e Farmacognosia, Università di Urbino, Italy.
Cattabeni
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F
Cantoni
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D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002455:Cell Division; D006224:Cricetinae; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D016521:Electrophoresis, Gel, Pulsed-Field; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010641:Phenotype
D004277:DNA, Single-Stranded; D006861:Hydrogen Peroxide