Increased DNA damage in hematopoietic cells of mice with graft-versus-host disease.
Patients who received hematopoietic cell transplants have an increased risk for a new malignancy. In addition to genotoxic regimens such as radiotherapy and chemotherapy, graft-versus-host disease (GVHD) is a risk factor for development of new malignancies in long-term survivors. To understand mechanisms underlying this malignant transformation, we evaluated genomic damage in several murine models of GVHD by enumerating reticulocytes containing micronuclei (MN) in the blood after semi-allogeneic (parent-into-F1) hematopoietic cell transplantation. On day 40 after transplantation, MN frequencies were significantly increased in unirradiated (C57BL6 x DBA/2) F1 (BDF1) and (BALB/c x C57BL6) F1 (CBF1) mice that received cells from C57BL6 (B6) donors. MN frequencies were not significantly increased in F1 mice that received cells from DBA/2 or BALB/c donors. Serum levels of tumor necrosis factor-alpha (TNF-alpha) were higher after transplantation with B6 donors than with DBA/2 or BALB/c donors. The results indicate that GVHD, without irradiation, can induce genomic damage associated with inflammatory reactions manifested by increased TNF-alpha levels.
Kusunoki
Yoichiro
Y
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732 0815, Japan. ykusunok@rerf.or.jp
Hamasaki
Kanya
K
Koyama
Kazuaki
K
Imai
Kazue
K
Hayashi
Tomonori
T
Martin
Paul J
PJ
Nakachi
Kei
K
D000818:Animals; D004249:DNA Damage; D005260:Female; D042822:Genomic Instability; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha