Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after gamma-irradiation.
Mouse strains exhibit different susceptibilities to gamma-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of gamma-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.
Maruyama
Masaki
M
Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan.
Yamamoto
Takashi
T
Kohara
Yuki
Y
Katsuragi
Yoshinori
Y
Mishima
Yukio
Y
Aoyagi
Yutaka
Y
Kominami
Ryo
R
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease / Q000209:etiology / Q000235:genetics; D008223:Lymphoma / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology*; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism* / Q000528:radiation effects*; D014157:Transcription Factors / Q000378:metabolism*; D000097809:Transcription Factor MTF-1
D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1