X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells

Li Liang, Li Deng, Marc S. Mendonca, Yanping Chen, Betty Zheng, Peter J. Stambrook, Changshun Shao, Jay A. Tischfield

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

There are a variety of mechanisms and pathways whereby cells safeguard their genomes in the face of environmental insults that damage DNA. Whether each of these pathways is equally robust at specific developmental stages in mammals and whether they are also modulated in a tissue-specific manner, however, are unclear. Here, we report that ionizing radiation (IR) produces different types of somatic mutations in fetal cells compared with adult cells of the same lineage. While 1 Gy of X-ray significantly induced intragenic point mutations in T cells of adult mice, no point mutational effect was observed when applied to fetuses. Fetal exposure to IR, on the other hand, led to a significant elevation of mitotic recombination in T cells, which was not observed in adults. Base excision repair (BER) activity was significantly lower in fetal hematopoietic cells than in adult cells, due to a low level of DNA polymerase β, the rate-limiting enzyme in BER. In fetal hematopoietic cells, this low BER activity, together with a high rate of proliferation, causes X-ray-induced DNA lesions, such as base damage, single strand breaks and double strand breaks, to be repaired by homologous recombination, which we observe as mitotic recombination. Higher BER activity and a relatively lower rate of cell proliferation likely contribute to the significant induction of DNA point mutations in adults. Thus, the mutational response to IR is at least partly determined by the availability of specific repair pathways and other developmentally regulated phenotypes, such as mitotic index.

Original languageEnglish (US)
Pages (from-to)1380-1385
Number of pages6
JournalDNA Repair
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2007

Keywords

  • Base excision repair
  • Developmental stage
  • Ionizing radiation
  • Mitotic recombination
  • Prenatal exposure

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Liang, L., Deng, L., Mendonca, M. S., Chen, Y., Zheng, B., Stambrook, P. J., Shao, C., & Tischfield, J. A. (2007). X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells. DNA Repair, 6(9), 1380-1385. https://doi.org/10.1016/j.dnarep.2007.04.005