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(PP341) Role of homologous recombination in the alpha particle bystander effect for sister chromatid exchanges and chromosomal aberrations.
Nagasawa, Hatsumi*,1, Peng, Yuanlin1, Wilson, Paul1, Lio, Yi-Ching2, Chen, David2, Bedford, Joel1, Little, John3, 1 Environmental and Radiological Health Sciences, Fort Collins, CO, United States2 Department of Radiation Oncology, Dallas, TX, United States3 Center for Radiation Sciences and Environmental Health, Boston, MA, United States
ABSTRACT- The bystander effect for sister chromatid exchanges (SCE) and chromosomal aberrations (CA) was examined in hamster cells lines deficient in either DNA-PKcs (V3 cells, deficient in non-homologous end joining, NHEJ) or Rad51C (irs3 cells, deficient in homologous recombination, HR). Cells synchronized in G0/G1 phase were irradiated with very low fluences of alpha particles such that <1% of the nuclei were traversed by an alpha particle. Wild-type cells showed a prominent bystander response for SCE induction; an even greater effect was observed in V3 cells. On the other hand, no significant induction of SCE was observed in the irs3 Rad51C-deficient bystander cells irradiated at various stages in the cell cycle. Whereas a marked bystander effect for CA occurred in V3 cells, the induction of CA in irs3 bystander cells was minimal and similar to that of wild-type cells. Based on these findings, we hypothesize that HR is essential for the induction of SCE in bystander cells; however, HR is unable to repair the DNA damage induced in NHEJ-deficient bystander cells that leads to either SCE or CA. Several additional mutant cell strains deficient in other HR proteins are currently being examined. This work was supported by grant DE-FG03-01ER63235 from the U.S. Department of Energy.
Key words: homologous recombination, bystander effect, alpha particle, SCE
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