title: Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.
abstract: It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Seishi
authors.initials: S
authors.lastname: Kyoizumi
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: b  Statistics and.
authors.forename: Munechika
authors.initials: M
authors.lastname: Misumi
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Kengo
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Kazue
authors.initials: K
authors.lastname: Imai
authors.affiliation: c  Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan; and.
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.affiliation: d  Departments of Medicine and Immunology and.
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Young
authors.affiliation: e  Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Jae-Hung
authors.initials: JH
authors.lastname: Shieh
authors.affiliation: e  Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Moore
authors.affiliation: d  Departments of Medicine and Immunology and.
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
authors.affiliation: a  Departments of Radiobiology/Molecular Epidemiology.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kusunoki
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000166:cytology* / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000528:radiation effects*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D054043:Nuclear Weapons / Q000706:statistics & numerical data*; D000069079:Radiation Exposure / Q000706:statistics & numerical data*; D017678:Sex Distribution; D017741:Survivors / Q000706:statistics & numerical data*