Abstract
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Article Information:
The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Experimental Pharmacology
Alexander A. Bukhvostov, Juri K. Napolov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov
Corresponding Author: Alexander A. Bukhvostov
Submitted: September 14, 2013
Accepted: September 25, 2013
Published: February 20, 2014 |
Abstract:
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Human acute myeloblast leukemia HL60 cells overexpresses 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/40 Ca substitution, a 2.25-fold enzyme inhibition has been shown to prove the 43 Ca-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 n-210 n DNA produced by either intact or 40 Ca-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: 40Ca and 43Ca isotopes, Acute Myeloblast Leukemia (AML), DNA Polymerase Beta (DNApolB), HL-60 cells, Magnetic Isotope Effect (MIE ), , ,
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Cite this Reference:
Alexander A. Bukhvostov, Juri K. Napolov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov, . The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Experimental Pharmacology. British Journal of Pharmacology and Toxicology, (1): 35-41.
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ISSN (Online): 2044-2467
ISSN (Print): 2044-2459 |
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