Processing of abasic DNA clusters in hApeI-silenced primary fibroblasts exposed to low doses of X-irradiation
Journal Article
·
· Journal of Biosciences
Clustered damage in DNA includes two or more closely spaced oxidized bases, strand breaks or abasic sites that are induced by high- or low-linear-energy-transfer (LET) radiation, and these have been found to be repair-resistant and potentially mutagenic. In the present study we found that abasic clustered damages are also induced in primary human fibroblast cells by low-LET X-rays even at very low doses. In response to the induction of the abasic sites, primary fibroblasts irradiated by low doses of X-rays in the range 10-100 cGy showed dose-dependent up-regulation of the DNA repair enzyme, ApeI. We found that the abasic clusters in primary fibroblasts were more lethal to cells when hApeI enzyme expression was down-regulated by transfecting primary fibroblasts with hApeI siRNA as determined by clonogenic survival assay. Endonuclease activity of hApeI was found to be directly proportional to hApeI gene-silencing efficiency. The DNA repair profile showed that processing of abasic clusters was delayed in hApeI-siRNA-silenced fibroblasts, which challenges the survival of the cells even at very low doses of X-rays. Thus, the present study is the first to attempt to understand the induction of cluster DNA damage at very low doses of low-LET radiation in primary human fibroblasts and their processing by DNA repair enzyme ApeI and their relation with the survival of the cells.
- Research Organization:
- BROOKHAVEN NATIONAL LABORATORY (BNL)
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 1025484
- Report Number(s):
- BNL--95385-2011-JA; KP1602020
- Journal Information:
- Journal of Biosciences, Journal Name: Journal of Biosciences Journal Issue: 1 Vol. 36; ISSN JOBSDN; ISSN 0250-5991
- Country of Publication:
- United States
- Language:
- English
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