TY - JOUR
T1 - Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination
AU - Nagasawa, Hatsumi
AU - Wilson, Paul F.
AU - Chen, David J.
AU - Thompson, Larry H.
AU - Bedford, Joel S.
AU - Little, John B.
N1 - Funding Information:
The authors would like to thank Jessica D. Caver, Zane H. Story, Christopher R. Larson, Dr. Yuanlin Peng and Dr. John Hinz for technical assistance and Dr. Yi-Ching Lio, Dr. Nan Liu, and Dr. Malgorzata Zdzienicka for providing cell lines. This research was supported by grants DE-FG02-07ER64350 (HN, JSB), DE-FG02-05ER65089 (JBL) and FWP SCW-0543 (PFW, LHT) from the U.S. Department of Energy Office of Biological and Environmental Research Low Dose Radiation Research Program and NCI/NIH grant CA112566 (PFW, LHT) from the U.S. Department of Health and Human Services. A portion of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells [H. Nagasawa, Y. Peng, P.F. Wilson, Y.C. Lio, D.J. Chen, J.S. Bedford, J.B. Little, Role of homologous recombination in the alpha-particle-induced bystander effect for sister chromatid exchanges and chromosomal aberrations, Radiat. Res. 164 (2005) 141-147]. In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23 to 0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after α-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.
AB - We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells [H. Nagasawa, Y. Peng, P.F. Wilson, Y.C. Lio, D.J. Chen, J.S. Bedford, J.B. Little, Role of homologous recombination in the alpha-particle-induced bystander effect for sister chromatid exchanges and chromosomal aberrations, Radiat. Res. 164 (2005) 141-147]. In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23 to 0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after α-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.
KW - Alpha particles
KW - BRCA2
KW - Bystander effect
KW - Homologous recombination
KW - Ionizing radiation
KW - Low dose
KW - Rad51 paralogs
KW - Sister chromatid exchange
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U2 - 10.1016/j.dnarep.2007.11.014
DO - 10.1016/j.dnarep.2007.11.014
M3 - Article
C2 - 18182331
AN - SCOPUS:39149100949
SN - 1568-7864
VL - 7
SP - 515
EP - 522
JO - DNA Repair
JF - DNA Repair
IS - 3
ER -