title: Biophysical studies of mutated K562 DNA (erythroleukemic cells) binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing binding behavior.
abstract: K562 cells are erythroleukemic cells derived from a chronic myeloid leukemia patient in blast crisis. Comparison of the genome from K562 cells and normal human genome has been very useful strategy, in uncovering eight genes, implicated in acute myeloid leukemia (AML). These genes carry mutations in K562 genome and the role of these mutations in the progression and treatment of AML is still not known. Consequences of these mutations on drug DNA binding are also not known exactly. In the present study, mutation induced structural changes in K562 genome, compared to normal genome, are identified by Fourier transform infra red (FTIR) and circular dichroism (CD) spectroscopy. These structural changes in native K562 DNA favor stronger binding with binding constants 2.0 × 10⁸ and 1.9 × 10⁹ M⁻¹ with antileukemic drugs adriamycin and daunomycin (DNM), respectively, compared to normal DNA. On binding, these drugs disrupt the native B form structure of normal DNA to a greater extent, compared to A-like structure of K562 DNA. Fluorescence and absorption studies reveal higher intercalation as well as mixed groove binding of these drugs with K562 DNA compared to normal DNA. Among the drugs, DNM has higher affinity for K562 DNA.
authors: School of Biotechnology and Biological Sciences, West Bengal University of Technology, BF-142, Sector I, Salt Lake, 700 064 Kolkata, India.
authors: Debjani
authors: D
authors: Ghosh
authors: Chabita
authors: C
authors: Saha
authors: Maidul
authors: M
authors: Hossain
authors: Subrata Kumar
authors: SK
authors: Dey
authors: Gopinatha Suresh
authors: GS
authors: Kumar
mesh_terms: D055592:Biophysical Phenomena; D002942:Circular Dichroism; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D004273:DNA, Neoplasm; D004317:Doxorubicin; D003630:Daunorubicin