J Vet Sci.  2013 Sep;14(3):271-279. 10.4142/jvs.2013.14.3.271.

Differential expression of thymic DNA repair genes in low-dose-rate irradiated AKR/J mice

• Bong JJ
• Kang YM
• Shin SC
• Choi SJ
• Lee KM
• Kim HS

• KMID: 1705557
• DOI: http://doi.org/10.4142/jvs.2013.14.3.271

Abstract

We previously determined that AKR/J mice housed in a low-dose-rate (LDR) (137Cs, 0.7 mGy/h, 2.1 Gy) gamma-irradiation facility developed less spontaneous thymic lymphoma and survived longer than those receiving sham or high-dose-rate (HDR) (137Cs, 0.8 Gy/min, 4.5 Gy) radiation. Interestingly, histopathological analysis showed a mild lymphomagenesis in the thymus of LDR-irradiated mice. Therefore, in this study, we investigated whether LDR irradiation could trigger the expression of thymic genes involved in the DNA repair process of AKR/J mice. The enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways showed immune response, nucleosome organization, and the peroxisome proliferator-activated receptors signaling pathway in LDR-irradiated mice. Our microarray analysis and quantitative polymerase chain reaction data demonstrated that mRNA levels of Lig4 and RRM2 were specifically elevated in AKR/J mice at 130 days after the start of LDR irradiation. Furthermore, transcriptional levels of H2AX and ATM, proteins known to recruit DNA repair factors, were also shown to be upregulated. These data suggest that LDR irradiation could trigger specific induction of DNA repair-associated genes in an attempt to repair damaged DNA during tumor progression, which in turn contributed to the decreased incidence of lymphoma and increased survival. Overall, we identified specific DNA repair genes in LDR-irradiated AKR/J mice.

Keyword

AKR/J mice; DNA repair genes; low-dose-rate radiation; thymic lymphoma

MeSH Terms

Animals
DNA Repair/*radiation effects
Dose-Response Relationship, Radiation
Female
Gene Expression Regulation/*radiation effects
Gene Regulatory Networks/radiation effects
Lymphoma/etiology/*genetics
Mice
Mice, Inbred AKR
Oligonucleotide Array Sequence Analysis
*Radiation, Ionizing
Reverse Transcriptase Polymerase Chain Reaction
Thymus Gland/*radiation effects
Thymus Neoplasms/etiology/*genetics

Figure

• 

  Fig. 1 Comparison of the relative thymus weight, and morphological changes among Sham-IR, HDR-IR, LDR-IR AKR/J mice. (A) Comparison of the relative thymus weights among Sham-IR, HDR-IR, LDR-IR AKR/J mice at day 130. (B) Hematoxylin and eosin staining revealed pleomorphic neoplastic cells with marked anisocytosis and anisokaryosis in the sham-IR and HDR-IR mice, whereas the cells and their nuclei were relatively small and uniform in size in the LDR-IR mice (×400). n = 8. Scale bars = 200 µm. Sham-IR: sham-irradiated, HDR-IR: high-dose-rate irradiated, LDR-IR: low-dose-rate irradiated.

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