Differential expression of immune-associated cancer regulatory genes in low- versus high-dose-rate irradiated AKR/J mice.
AKR/J mice carrying leukemia viral inserts develop thymic lymphoma. Recently, we demonstrated that the incidence of thymic lymphoma was decreased when these mice were raised in a low-dose-rate γ-irradiation facility. In contrast, mice irradiated at a high-dose rate developed severe thymic lymphoma and died much earlier. To understand the genetic changes occurred by low- versus high-dose-rate γ-irradiation whole genome microarray was performed. Both groups of mice demonstrated up-regulation of Ifng, Igbp1, and IL7 in their thymuses, however, mice exposed to high-dose-rate γ-irradiation exhibited marked down-regulation of Sp3, Il15, Traf6, IL2ra, Pik3r1, and Hells. In contrast, low-dose-rate irradiated mice demonstrated up-regulation of Il15 and Jag2. These gene expression profiles imply the impaired immune signaling pathways by high-dose-rate γ-irradiation while the facilitation of anti-tumor immune responses by low-dose-rate γ-irradiation. Therefore, our data delineate common and distinct immune-associated pathways downstream of low- versus high-dose-rate irradiation in the process of cancer progression in AKR/J mice.
Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., SSangmun-dong, Dobong-gu, Seoul, Republic of Korea.
Suk Chul
SC
Shin
Kyung-Mi
KM
Lee
Yu Mi
YM
Kang
Kwanghee
K
Kim
Seon Ah
SA
Lim
Kwang Hee
KH
Yang
Ji Young
JY
Kim
Seon Young
SY
Nam
Hee Sun
HS
Kim
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000528:radiation effects*; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008822:Mice, Transgenic; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D013950:Thymus Gland / Q000276:immunology / Q000528:radiation effects*; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology; D014916:Whole-Body Irradiation