A sensitivity to oxidative stress is linked to chromosome 11 but is not due to a difference in single strand DNA breakage or repair.
Defects in loci on chromosome 11 have been associated with tumourigenicity, anchorage-independent growth, metastasis and radiosensitive DNA repair in tumour cells. The introduction of normal chromosome 11 into these cells suppresses these responses. In the present study we tested two hypotheses: (1) that microcell fusion of normal chromosome 11 into bladder-carcinoma cells (A1698) can protect the cells against chromosomal damage by oxidative stress; and (2) that insertion of normal chromosome 11 corrects a single-strand (SS) DNA-repair defect. Cultures of A1698 (termed parent) and its microcell-mediated hybrid (termed hybrid) were exposed for 1 h to xanthine/xanthine oxidase (X/XO) or co-incubated with human neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Micronucleus frequencies (an indication of chromosomal damage) were significantly higher in parent cultures after treatment than in hybrid (P < 0.0001). The level of single-strand DNA breakage and its repair was assayed in X/XO-treated cultures with the alkaline comet assay. There was no significant difference between parent and hybrid in the amount of SS DNA breakage at treatment (P > 0.1) or after 20 min of repair (P > 0.1). The data support the involvement of a defect in chromosome 11 leading to sensitivity to oxidative stress and suggest this defect is not in the initial amount or rate of rejoining of SS DNA breakage.
Ward
A J
AJ
British Columbia Cancer Research Centre, Vancouver, Canada.
Olive
P L
PL
Burr
A H
AH
Rosin
M P
MP
D002460:Cell Line; D002880:Chromosomes, Human, Pair 11; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D015162:Micronucleus Tests; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D019820:Xanthine; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate