TY - JOUR
T1 - Doxorubicin-induced DNA breaks, topoisomerase II activity and gene expression in human melanoma cells
AU - Ramachandran, Cheppail
AU - Samy, T. S.Anantha
AU - Xiao Ling Huang, Ling Huang
AU - Zhao Kang Yuan, Kang Yuan
AU - Krishan, Awtar
PY - 1993/3/24
Y1 - 1993/3/24
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-2952(93)90293-6
DO - 10.1016/0006-2952(93)90293-6
M3 - Article
C2 - 8385463
AN - SCOPUS:0027537489
VL - 45
SP - 1367
EP - 1371
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 6
ER -