The objective of the proposed research is to elucidate the implications of densely ionizing radiations emitted by diagnostic and therapeutic radionuclides (Auger electrons and alpha particles) for both radiation protection and cancer therapy. We intend to explore mechanisms producing DNA damage in well-characterized simple systems (plasmids) and in higher order chromatin structures (mammalian cell nuclei) and assess the consequence of spatial positioning of the decaying nuclide (ascertained by computational modeling methods) as well as changes in the surrounding environment. We also plan to determine the quantitative relationships between microscopic dose and detrimental biologic effects by (i) associating radionuclide-decay-induced apoptosis with the physical decay characteristics of these radionuclides, their site of decay, cell type, and cell radiosensitivity; (ii) investigating the bystander effect in fn-vivo tumor models; (iii) assessing the mutagenic response to the decay of these radionuclides following cytoplasmic localization and examining whether this is a consequence of direct or indirect mechanisms; and (iv) determining doses that lead to alterations in gene expression and neoplastic transformation in normal mammalian cells. Finally, we will exploit an animal tumor model as a preclinical system for determining the utility of the thymidine analog 5-[12Sl]iodo-2'-deoxyuridine in cancer therapy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Wong, Rosemary S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Medicine
United States
Zip Code
Balagurumoorthy, Pichumani; Xu, Xiang; Wang, Ketai et al. (2012) Effect of distance between decaying (125)I and DNA on Auger-electron induced double-strand break yield. Int J Radiat Biol 88:998-1008
Mamlouk, Omar; Balagurumoorthy, Pichumani; Wang, Ketai et al. (2012) Bystander effect in tumor cells produced by Iodine-125 labeled human lymphocytes. Int J Radiat Biol 88:1019-27
Kassis, Amin I (2011) Molecular and cellular radiobiological effects of Auger emitting radionuclides. Radiat Prot Dosimetry 143:241-7
Balagurumoorthy, Pichumani; Adelstein, S James; Kassis, Amin I (2011) Novel method for quantifying radiation-induced single-strand-break yields in plasmid DNA highlights 10-fold discrepancy. Anal Biochem 417:242-6
Zhu, Xuping; Palmer, Matthew R; Makrigiorgos, G Mike et al. (2010) Solid-tumor radionuclide therapy dosimetry: new paradigms in view of tumor microenvironment and angiogenesis. Med Phys 37:2974-84
Singh, Amarjit; Yang, Yongliang; Adelstein, S James et al. (2008) Synthesis and application of molecular probe for detection of hydroxyl radicals produced by Na(125)I and gamma-rays in aqueous solution. Int J Radiat Biol 84:1001-10
Balagurumoorthy, Pichumani; Adelstein, S James; Kassis, Amin I (2008) Method to eliminate linear DNA from mixture containing nicked circular, supercoiled, and linear plasmid DNA. Anal Biochem 381:172-4
Balagurumoorthy, Pichumani; Chen, Kai; Adelstein, S James et al. (2008) Auger electron-induced double-strand breaks depend on DNA topology. Radiat Res 170:70-82
Kassis, Amin I (2008) Therapeutic radionuclides: biophysical and radiobiologic principles. Semin Nucl Med 38:358-66
Balagurumoorthy, Pichumani; Wang, Ketai; Adelstein, S James et al. (2008) DNA double-strand breaks induced by decay of (123)I-labeled Hoechst 33342: role of DNA topology. Int J Radiat Biol 84:976-83

Showing the most recent 10 out of 81 publications