title: Array-CGH analyses of murine malignant lymphomas: genomic clues to understanding the effects of chronic exposure to low-dose-rate gamma rays on lymphomagenesis.
abstract: We previously reported that mice chronically irradiated with low-dose-rate gamma rays had significantly shorter mean life spans than nonirradiated controls. This life shortening appeared to be due primarily to earlier death due to malignant lymphomas in the irradiated groups (Tanaka et al., Radiat. Res. 160, 376-379, 2003). To elucidate the molecular pathogenesis of murine lymphomas after low-dose-rate irradiation, chromosomal aberrations in 82 malignant lymphomas from mice irradiated at a dose rate of 21 mGy/day and from nonirradiated mice were compared precisely by microarray-based comparative genomic hybridization (array-CGH) analysis. The array carried 667 BAC clones densely selected for the genomic regions not only of lymphoma-related loci but also of surface antigen receptors, enabling immunogenotyping. Frequent detection of the apparent loss of the Igh region on chromosome 12 suggested that most lymphomas in both groups were of B-cell origin. Array-CGH profiles showed a frequent gain of whole chromosome 15 in lymphomas predominantly from the irradiated group. The profiles also demonstrated copy-number imbalances of partial chromosomal regions. Partial gains on chromosomes 12, 14 and X were found in tumors from nonirradiated mice, whereas losses on chromosomes 4 and 14 were significantly associated with the irradiated group. These findings suggest that lymphomagenesis under the effects of continuous low-dose-rate irradiation is accelerated by a mechanism different from spontaneous lymphomagenesis that is characterized by the unique spectrum of chromosomal aberrations.
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, 2-121, Hacchazawa, Takahoko, Rokkasho, Aomori 039-3213, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takabatake
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tokuhisa
authors.initials: T
authors.lastname: Hirouchi
authors.forename: Masako
authors.initials: M
authors.lastname: Nakamura
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Ignacia
authors.initials: I
authors.lastname: Braga-Tanaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ichinohe
authors.forename: Mikio
authors.initials: M
authors.lastname: Saitou
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oghiso
authors.forename: Kimio
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D017403:In Situ Hybridization; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011829:Radiation Dosage