Menadione-induced DNA damage in a human tumor cell line

Emily O. Ngo, Ter Ping Sun, Jang Yang Chang, Chang Chung Wang, Kwan Hwa Chi, Ann Lii Cheng, Louise M. Nutter

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The nature and extent of menadione (MD)-induced DNA damage were explored using the human breast cancer cell line MCF-7. Concentration-dependent single-strand (ss) and double-strand (ds) DNA breaks were detected in MD-treated MCF-7 cells using the alkaline- and neutral-elution techniques, respectively. The repair of ss and ds DNA breaks was extensive but not complete after a 6-hr incubation in drug-free medium. Evidence was found for the production of DNA interstrand crosslinks in MCF-7 cells treated with the bifunctional alkylating agent, mitomycin C, but not for cells treated with MD. Exposure of MCF-cells to etoposide (VP-16), mitoxantrone and camptothecin resulted in the detection of significant amounts of protein-linked DNA breaks, whereas none were found in MD-treated cells. These results support the proposition that MD-induced DNA damage is not likely to be mediated via topoisomerases, nor do significant amounts of protein-linked DNA form in MD-treated cells. Thus, MD serves as a good model for examination of the role of the quinone moiety in DNA damage in relation to redox cycling. Future studies directed at elucidation of the biochemical determinants mediating formation of reactive oxygen species effecting the MD-induced DNA damage are necessary and underway.

Original languageEnglish
Pages (from-to)1961-1968
Number of pages8
JournalBiochemical Pharmacology
Volume42
Issue number10
DOIs
Publication statusPublished - 1991 Oct 24

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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  • Cite this

    Ngo, E. O., Sun, T. P., Chang, J. Y., Wang, C. C., Chi, K. H., Cheng, A. L., & Nutter, L. M. (1991). Menadione-induced DNA damage in a human tumor cell line. Biochemical Pharmacology, 42(10), 1961-1968. https://doi.org/10.1016/0006-2952(91)90596-W