A sensitivity to oxidative stress is linked to chromosome 11 but is not due to a difference in single strand DNA breakage or repair
Ward, A.J.; Olive, P.L.; Burr, A.H.; Rosin, M.P.
Mutation Research 294(3): 299-308
1993
ISSN/ISBN: 0027-5107 PMID: 7692269 Document Number: 416512
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 lt 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 gt 0.1) or after 20 min of repair (P gt 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.