Abstract
Mice chronically irradiated with gamma-ray at a low dose rate (21mGy/day, 400 dyas) had significantly shorter life spans compared to the nonirradiated controls. The major cause for this life shortening was considered to be the earlier genesis and/or the faster progression of malignant lymphomas in the irradiated group. In the present study, chromosomal aberrations in 82 malignant lymphomas were analyzed by array-CGH method and were compared between the nonirradiated and the irradiated groups. Many array-CGH profiles showed numeric aberrations of whole-chromosome, of which trisomy 15 was most frequent in the irradiated group, as well as copy-number imbalances of partial chromosomal regions. Most of them are syntenic to human chromosomal regions frequently showing aberrations in human lymphomas, suggesting an involvement of common molecular pathogenesis. Gains on chromosomes 12 (p=0.005) and X (p=0.084) were associated preferentially with the nonirradiated group, while gain on chromosomes 11 (p=0.057) and losses on chromosomes 4 (p=0.088) and 14 (p=0.026) were detected more frequently in the irradiated group. Notably, recurrent aberrations detected in the irradiated group involved the following genes, such as c-myc , p16INK4a, p73, Rel and RB, where their dysfunctions or copy-number alterations were considered to confer increased aggressivity and proliferative advantage in human lymphomas. These findings suggest a possibility that highly aggressive lymphomas might develop preferentially in the irradiated group. This work was supported by grants from Aomori Prefecture, Japan.
