Doxorubicin-induced DNA breaks, topoisomerase II activity and gene expression in human melanoma cells

Cheppail Ramachandran, T. S.Anantha Samy, Ling Huang Xiao Ling Huang, Kang Yuan Zhao Kang Yuan, Awtar Krishan

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

We have analyzed five human melanoma cell lines, displaying variable doxorubicin resistance (1- to 6-fold), for drug-induced DNA breaks, topoisomerase II activity and mRNA expression. Enhanced drug efflux was not the reason for doxorubicin resistance of these tumor cells although they overexpressed the transmembrane 170 kDa P-glycoprotein. Doxorubicin-induced DNA lesions (2-fold) and topoisomerase II activity (7-fold) were higher in HM-1 and G361 cells than in the less doxorubicin-sensitive NH and FCCM-9 cells. Topoisomerase II mRNA expression was also 2-fold higher in HM-1 and G361 cells. Doxorubicin-induced DNA breaks and topoisomerase II activity inversely correlated with the degree of doxorubicin sensitivity. Southern blot analysis showed variation in the hybridization pattern of topoisomerase II gene in doxorubicin-resistant cells when compared to sensitive cells. This study portrays the low doxorubicin sensitivity of NH and FCCM-9 cells as "atypical" and emphasizes the importance of DNA damage and topoisomerase II activity in cellular low doxorubicin resistance.

Original languageEnglish (US)
Pages (from-to)1367-1371
Number of pages5
JournalBiochemical Pharmacology
Volume45
Issue number6
DOIs
StatePublished - Mar 24 1993

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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    Ramachandran, C., Samy, T. S. A., Xiao Ling Huang, L. H., Zhao Kang Yuan, K. Y., & Krishan, A. (1993). Doxorubicin-induced DNA breaks, topoisomerase II activity and gene expression in human melanoma cells. Biochemical Pharmacology, 45(6), 1367-1371. https://doi.org/10.1016/0006-2952(93)90293-6