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Abstract
Purpose: Exposure of sublethal doses of ionizing radiation can induce protective mechanisms against a subsequent higher dose irradiation. This phenomenon, called radiation-induced adaptive response (AR), has been described in a wide range of biological models. We previously demonstrated the existence of AR in mice during late organogenesis. In this study, we investigated molecular mechanisms underlying AR in this model.
Materials and methods: Using DNA microarrays, we performed a global analysis of transcriptome regulations in adapted and non-adapted cells collected from whole mouse fetuses, after in utero exposure to priming irradiation.
Results: We identified AR-specific gene modulations. Our results suggested the involvement of signal transduction and Tumor protein (p53)-related pathways in the induction of AR.
Conclusions: Our results are in agreement with previous investigations showing that AR could be dependant on p53 activity. The observed gene modulations may also have possible consequences for subsequent developmental process of the fetus. This is the first report of AR-specific modulations at the molecular level in utero, which could serve as a basis for subsequent studies aimed at understanding AR in this model and possible long-term effects.
| Abbreviations | ||
| AR | = | Adaptive response |
| NAR | = | Non-Adaptive Response |
| AER | = | Average Expression Ratio |
| DSB | = | Double Strand Break |
| p53 | = | Tumor protein 53 |
| MnSOD | = | Manganese superoxide dismutase |
| Rad51 | = | RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) |
| Rad54 | = | RAD54 like (S. cerevisiae) |
| BRCA1 | = | Breast cancer 1 |
| RT-PCR | = | Reverse transcription polymerase chain reaction |
| NF-κB | = | Nuclear transcription factor kappa B |
| Csf1 | = | Colony stimulating factor 1 |
| Fgf22 | = | Fibroblast growth factor 22 |
| CNS | = | Central nervous system |
| GPCRDB | = | G protein-coupled receptor database |
| Pdgfa | = | Platelet derived growth factor, alpha |
| Aak1 | = | AP2-associated protein kinase 1 |
| ALDh1a3 | = | Aldehyde dehydrogenase family 1, subfamily A3 |
| Fez1 | = | Fasciculation and elongation protein zeta 1 |
| Mtmr9 | = | Myotubularin related protein 9 |
| Pcdhb14 | = | Protocadherin beta 14 |
| Cacna1a | = | Voltage-dependent P/Q-type calcium channel alpha-1A subunit |
| Csnk2a1 | = | Casein Kinase 2, Alpha |
| Ptprc | = | Protein tyrosine phosphatase, receptor type, C |
| Rhobtb3 | = | Rho-related BTB domain containing 3 |
| Inhbe | = | Inhibin beta E |
| Tead3 | = | TEA domain family member 3 |
| Foxb1 | = | Forkhead Box B1 |
| Foxn1 | = | Forkhead Box N1 |
| Sgce | = | Sarcoglycan, epsilon |
| Wnt | = | Wingless-type MMTV integration site family |
| EGF | = | Epidermal growth factor |
| TGF | = | Transforming growth factor |
| Aldh1a3 | = | Aldehyde dehydrogenase family 1, subfamily A3 |
| CK2 | = | Casein kinase 2 |
| Bax | = | B-cell leukemia/lymphoma 2 (BCL2)-associated protein |
| p21 | = | protein 21 |
| Abbreviations | ||
| AR | = | Adaptive response |
| NAR | = | Non-Adaptive Response |
| AER | = | Average Expression Ratio |
| DSB | = | Double Strand Break |
| p53 | = | Tumor protein 53 |
| MnSOD | = | Manganese superoxide dismutase |
| Rad51 | = | RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) |
| Rad54 | = | RAD54 like (S. cerevisiae) |
| BRCA1 | = | Breast cancer 1 |
| RT-PCR | = | Reverse transcription polymerase chain reaction |
| NF-κB | = | Nuclear transcription factor kappa B |
| Csf1 | = | Colony stimulating factor 1 |
| Fgf22 | = | Fibroblast growth factor 22 |
| CNS | = | Central nervous system |
| GPCRDB | = | G protein-coupled receptor database |
| Pdgfa | = | Platelet derived growth factor, alpha |
| Aak1 | = | AP2-associated protein kinase 1 |
| ALDh1a3 | = | Aldehyde dehydrogenase family 1, subfamily A3 |
| Fez1 | = | Fasciculation and elongation protein zeta 1 |
| Mtmr9 | = | Myotubularin related protein 9 |
| Pcdhb14 | = | Protocadherin beta 14 |
| Cacna1a | = | Voltage-dependent P/Q-type calcium channel alpha-1A subunit |
| Csnk2a1 | = | Casein Kinase 2, Alpha |
| Ptprc | = | Protein tyrosine phosphatase, receptor type, C |
| Rhobtb3 | = | Rho-related BTB domain containing 3 |
| Inhbe | = | Inhibin beta E |
| Tead3 | = | TEA domain family member 3 |
| Foxb1 | = | Forkhead Box B1 |
| Foxn1 | = | Forkhead Box N1 |
| Sgce | = | Sarcoglycan, epsilon |
| Wnt | = | Wingless-type MMTV integration site family |
| EGF | = | Epidermal growth factor |
| TGF | = | Transforming growth factor |
| Aldh1a3 | = | Aldehyde dehydrogenase family 1, subfamily A3 |
| CK2 | = | Casein kinase 2 |
| Bax | = | B-cell leukemia/lymphoma 2 (BCL2)-associated protein |
| p21 | = | protein 21 |