title: Radiation-dose response of glycophorin A somatic mutation in erythrocytes associated with gene polymorphisms of p53 binding protein 1.
abstract: Information on individual variations in response to ionizing radiation is still quite limited. Previous studies of atomic-bomb survivors revealed that somatic mutations at the glycophorin A (GPA) gene locus in erythrocytes were significantly elevated with radiation exposure dose, and that the dose response was significantly higher in survivors with subsequent cancer development compared to those without cancer development. Noteworthy in these studies were great inter-individual differences in GPA mutant fraction even in persons with similar radiation doses. It is hypothesized that persistent GPA mutations in erythrocytes of atomic-bomb survivors are derived from those in long-lived hematopoietic stem cell (HSC) populations, and that individual genetic backgrounds, specifically related to DNA double-strand break repair, contribute to individual differences in HSC mutability following radiation exposure. Thus, we examined the relationship between radiation exposure, GPA mutant fraction in erythrocytes, and single nucleotide polymorphisms (SNPs) of the key gene involved in DNA double-strand break repair, p53 binding protein 1 (53BP1). 53BP1 SNPs and inferred haplotypes demonstrated a significant interaction with radiation dose, suggesting that radiation-dose response of GPA somatic mutation is partly dependent on 53BP1 genotype. It is also possible that 53BP1 plays a significant role in DNA double-strand break repair in HSCs following radiation exposure.
authors.affiliation: Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan. kyoshi@rerf.or.jp
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: John B
authors.initials: JB
authors.lastname: Cologne
authors.forename: Seishi
authors.initials: S
authors.lastname: Kyoizumi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Maki
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D001853:Bone Marrow; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D006021:Glycophorins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009689:Nuclear Warfare; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011839:Radiation, Ionizing; D017741:Survivors; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D006021:Glycophorins; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: 53BP1; GPA Mf; Gene polymorphism; HSC; Radiation; Somatic mutation; glycophorin A mutant fraction; hematopoietic stem cell; p53 binding protein 1