Induction of chromosomal instability by chronic oxidative stress.
Earlier studies using GM10115 cells analyzed the capability of different DNA-damaging agents to induce genomic instability and found that acute oxidative stress was relatively inefficient at eliciting a persistent destabilization of chromosomes. To determine whether this situation would change under chronic exposure conditions, the human-hamster hybrid line GM10115 was cultured under conditions of oxidative stress. Chronic treatments consisted of 1-hour incubations using a range of hydrogen peroxide (25-200 microM) or glucose oxidase (GO; 5-50 mU/ml) concentrations that were administered once daily over 10 to 30 consecutive days. The toxicity of chronic treatments was modest (- one log kill) and consistent with the low yield of first division aberrations (<5%). However, analysis of over 180 clones and 36,000 metaphases indicated that chronic oxidative stress led to a high incidence of chromosomal instability. Treatment of cells with 100 and 200 microM hydrogen peroxide or 50 mU/ml GO was found to elicit chromosomal instability in 11%, 22%, and 19% of the clones analyzed, respectively. In contrast, control clones isolated after mock treatment did not show signs of chromosomal destabilization. These data suggest that chronic oxidative stress constitutes a biochemical mechanism capable of disrupting the genomic integrity of cells.
D000818:Animals; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005949:Glucose Oxidase / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D018384:Oxidative Stress; D013997:Time Factors
D006861:Hydrogen Peroxide; D005949:Glucose Oxidase