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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

Fingerprint

Repair
DNA Repair
X-Rays
Ionizing radiation
X rays
Mutation
Ionizing Radiation
T-cells
Point Mutation
Genetic Recombination
DNA
T-Lymphocytes
Mitotic Index
Mammals
Homologous Recombination
Cell proliferation
Cell Lineage
DNA-Directed DNA Polymerase
DNA Damage
Fetus

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Liang, L., Deng, L., Mendonca, M., Chen, Y., Zheng, B., Stambrook, P. J., ... 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

X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells. / Liang, Li; Deng, Li; Mendonca, Marc; Chen, Yanping; Zheng, Betty; Stambrook, Peter J.; Shao, Changshun; Tischfield, Jay A.

In: DNA Repair, Vol. 6, No. 9, 01.09.2007, p. 1380-1385.

Research output: Contribution to journalArticle

Liang, L, Deng, L, Mendonca, M, Chen, Y, Zheng, B, Stambrook, PJ, Shao, C & Tischfield, JA 2007, 'X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells', DNA Repair, vol. 6, no. 9, pp. 1380-1385. https://doi.org/10.1016/j.dnarep.2007.04.005
Liang, Li ; Deng, Li ; Mendonca, Marc ; Chen, Yanping ; Zheng, Betty ; Stambrook, Peter J. ; Shao, Changshun ; Tischfield, Jay A. / X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cells. In: DNA Repair. 2007 ; Vol. 6, No. 9. pp. 1380-1385.
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