Brookhaven National Laboratory - Past Employee
Department of Pharmacology
Basic Science Tower
Level 8, Room 140
Stony Brook University
Stony Brook, NY 11794-8651
Past Research Interests
A) Increased radio sensitization of glioma cell lines by lucanthone (and its structural
analogue hycanthone) due to direct physical destabilization of DNA base excision repair enzyme
Apurinic endonuclease1 (Ape1).
I am studying the dose response of glioma cell lines to low LET
radiation in terms of DNA damage repair and ATP release, in order to determine if there is any
correlation between DNA damage repair, radio-resistance and synaptic activity of these glioma cell lines. In this work,
our experimental objective has been to determine the effect of low LET radiation on base excision
repair enzyme, Apurinic Endonuclease-1 (Ape1) in glioma cell lines in presence of lucanthone, an
anti-cancer drug (in phase II clinical trials) used to treat brain tumors in conjunction with
radiotherapy. In this study I find that Ape1 endonuclease activity decreases in presence of
lucanthone and this decrease can be correlated to decreased clonogenic survival of glioma cell lines.
Interestingly, I find decreased Ape1 activity in glioma cell lines' cell extracts treated with
increasing concentration of lucanthone in presence of protease inhibitor cocktail, indicative of
lucanthone's degradative effects on Ape1. My collaboration with Rakhi Agarwal of Structural
Biology group at BNL has yielded an Ape1 structure with an unknown hydrophobic site where lucanthone
can possibly dock. Currently molecular docking/ dynamics studies are in progress for Ape1-lucanthone
interaction. We have also established that Ape1 over expression in radiosensitive glioma cell line
increases its radioresistance. In addition to these studies, Ape1 siRNA inhibition studies are in
B) Effect of low and high LET radiation on Apurinic Endonuclease-1 (Ape1) activity in glial progenitor
It is crucial to study the effect of ionizing radiations on nervous system due to the
deleterious effects of low/ high radiations encountered by brain tumor patients or by astronauts
in space. One of the main goals of NASA’s biological research is to advance the understanding
of the response mechanisms to radiation-caused DNA damage. Earlier radiation studies on the CNS
predominantly focused on neurons, with scant studies directly addressing the role of glial cells.
Hence, we will focus our research on determining the major DNA repair pathways induced in these cells.
We will study the effects of low/ high LET radiation on Ape1 in a OPC-like cell, the central glia-4
(CG-4), a rat bi-potential glial progenitor cell that can differentiate into OL or astrocytes. This project
is funded by NASA for three years.
Naidu M.D., Agarwal R., Pena L.A., Cunha L., Mezei M., Shen M., Wilson D.M. 3rd, Liu Y., Sanchez Z., Chaudhary P., Wilson S.H., and Waring M.J.
Lucanthone and Its Derivative Hycanthone Inhibit Apurinic Endonuclease-1 (APE1) by Direct Protein Binding.
PLoS One., 6(9):e23679. Epub 2011 Sep 15 (2011).
Naidu M.D., Mason J. M., Fung H., and Pena L.
Radiation resistance in human glioma cell lines is determined by the DNA damage repair activity of apurinic endonuclease 1 (Ape1).
(accepted in J.R.R. in Dec 2009).
Wang, H., Liu, S., Zhang, P., Zhang, S., Naidu M.D., Wang, H., and Wang, Y.
S-phase cells are more radiosensitive to high linear energy transfer radiation.
Intl. J. Rad. Oncol. Bio. Phys., 74(4):1236-1241 (2009).
Agarwal R. and Naidu M.D.
Crystal structure of hApe1 in a new crystal form with a bound ligand: Implications on catalytic mechanism and its inhibition
(PDB ID 2ISI, Deposition: 10/17/2006, Release: 10/31/2006)
Mason J., Naidu M.D., Barcia M., Porti D., Chavan S.S. and Chu C.C.
IL-4-induced gene-1 is a leukocyte L-amino acid oxidase with an unusual acidic pH preference and lysosomal localization.
J. Immunology, 173(7):4561-4567 (2004).
Naidu M.D. and Chander R.
Immunomodulation of macrophages by radiodetoxified LPS of Salmonella typhimurium.
Indian J. Exp. Biol., 37(3):283-289 (1999).
Naidu M.D., Chander R. and Nair P.M.
Effect of gamma irradiation on chemical and biological properties of lipopolysaccharide from Salmonella typhimurium.
Indian J. Exp. Biol., 36(6):588-592 (1998).
Kumthekar* M.M. and Katyare S.S.
Altered kinetic attributes of Na++K+-ATPase activity in kidney, brain and erythrocyte membranes in alloxan-diabetic rats.
Indian J. Exp. Biol., 30:26-32 (1992) (* Maiden Name).
Last Modified: July 11, 2012
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