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Abstract
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Article Information:
The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Therapies
Alexander A. Bukhvostov, Oleg A. Shatalov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov
Corresponding Author: Dmitry A. Kuznetsov
Submitted: September 15, 2013
Accepted: October 06, 2013
Published: February 20, 2014 |
Abstract:
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Human acute myeloblast leukemia HL60 cells over expresses a beta-type DNA polymerase (EC 2.7.7.7) which is found to be operated by Magnetic Isotope Effect (MIE) of Calcium once the Mg2+ ions replaced with the stable 43Ca2+ isotopes inside the enzyme catalytic sites. The isotopes mentioned are the only paramagnetic species of the Calcium isotopic set with a 0.135 natural abundance value and the negative 7/2 nuclear spin providing a nuclear magnetic moment equal to 1.317 Bohr magnetons. As compared to the Mg/40Ca substitution, a 2.25-fold enzyme inhibition has been shown to prove the 43Ca-MIE dependent mode of the catalysis turning down. This 43Ca-promoted enzyme hyper-suppression leads to a residual synthesis of shorted DNA fragments that counts 25-35 nucleotides in length contrasting with the 180-210 n DNA produced by either intact or 40Ca-loaded polymerase. Being occurred simultaneously with a marked MIE-promoted enzyme inhibition, this fact itself makes possible to consider these short (“size-invalid”) DNA segments hardly efficient in the DNA base-excision repair. The latter is a survival factor in leukemic cells where the DNApol&beta was found over expressed. That confirms a concept considering the DNApol&beta a legitimate target for antitumor agents since its inhibition deprives the malignant cell from a DNA base-excision repair in neoplasma. A possible trend making role of these data for molecular pharmacology of cancers is in a focus.
Key words: Acute Myeloblast Leukemia (AML), 40Ca and 43Ca isotopes, DNA polymerase Beta (DNApolB), Magnetic Isotope Effect (MIE), HL-60 cells, ,
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Cite this Reference:
Alexander A. Bukhvostov, Oleg A. Shatalov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov , . The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Therapies. British Journal of Pharmacology and Toxicology, (1): 42-48.
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ISSN (Online): 2044-2467
ISSN (Print): 2044-2459 |
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