Increased levels of p53 and PARP-1 in EL-4 cells probably related with the immune adaptive response induced by low dose ionizing radiation in vitro.

OBJECTIVE This paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit (DNA-PKcs) and PARP-1 genes in the LDR-induced AR in EL-4 cells. METHODS The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays (inductive dose, D1) and the succeeding high dose irradiation (challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively) with or without wortmannin (inhibitor of ATM and DNA-PK) and 3-aminobenzamid (inhibitor of PARP-1). And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. RESULTS The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 + D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB + D2 and the 3-AB + D1 + D2 groups were much lower than those in the D2 and the D1 + D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB + D1 + D2 groups was much higher than that in the D1 + D2 groups, that in the G₀/G₁ and the G₂ + M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin + D1 + D2 groups were much lower than those in the D1 + D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin + D1 + D2 and the D1 + D2 groups. CONCLUSION PARP-1 and p53 might play important roles in AR induced by LDR.

[1]  A. Takahashi,et al.  Radiation-induced adaptive responses and bystander effects. , 2004, Uchu Seibutsu Kagaku.

[2]  Hiroshi Suzuki,et al.  Poly(ADP-ribose) polymerase-1 inhibits ATM kinase activity in DNA damage response. , 2004, Biochemical and biophysical research communications.

[3]  S. Wolff,et al.  Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. , 1984, Science.

[4]  K. Ishizaki,et al.  DNA damage response pathway in radioadaptive response. , 2002, Mutation research.

[5]  M. Garmyn,et al.  Adaptive response of the skin to UVB damage: role of the p53 protein , 2006, International journal of cosmetic science.

[6]  J. Nickoloff,et al.  Regulation of DNA double-strand break repair pathway choice , 2008, Cell Research.

[7]  George Iliakis,et al.  Repair of radiation induced DNA double strand breaks by backup NHEJ is enhanced in G2. , 2008, DNA repair.

[8]  L. Declercq,et al.  A low UVB dose, with the potential to trigger a protective p53-dependent gene program, increases the resilience of keratinocytes against future UVB insults. , 2005, The Journal of investigative dermatology.

[9]  S. Tapio,et al.  Radioadaptive response revisited , 2007, Radiation and environmental biophysics.

[10]  Yang Xu DNA damage: a trigger of innate immunity but a requirement for adaptive immune homeostasis , 2006, Nature Reviews Immunology.

[11]  R. Mitchel,et al.  Low Doses of Radiation are Protective in vitro and in vivo: Evolutionary Origins , 2006, Dose-response : a publication of International Hormesis Society.

[12]  L. Feinendegen,et al.  Whole-body responses to low-level radiation exposure: new concepts in mammalian radiobiology. , 2007, Experimental hematology.

[13]  J. Schwartz Variability: the common factor linking low dose-induced genomic instability, adaptation and bystander effects. , 2007, Mutation research.

[14]  Leif E. Peterson,et al.  Low-Dose Irradiation Alters the Transcript Profiles of Human Lymphoblastoid Cells Including Genes Associated with Cytogenetic Radioadaptive Response , 2005, Radiation research.

[15]  G. Dianov,et al.  Poly(ADP-ribose) polymerase-1 modulates DNA repair capacity and prevents formation of DNA double strand breaks. , 2008, DNA repair.

[16]  G. Dianov,et al.  Poly ADP-ribose polymerase-1: an international molecule of mystery. , 2008, DNA repair.

[17]  L E Feinendegen,et al.  Evidence for beneficial low level radiation effects and radiation hormesis. , 2005, The British journal of radiology.

[18]  G. Raaphorst,et al.  Evaluation of adaptive responses to cisplatin in normal and mutant cell lines with mutations in recombination repair pathways. , 2006, Anticancer research.

[19]  B. Scott,et al.  Sparsely Ionizing Diagnostic and Natural Background Radiations are Likely Preventing Cancer and other Genomic-Instability-Associated Diseases , 2007, Dose-response : a publication of International Hormesis Society.

[20]  I. Szumiel Adaptive response: stimulated DNA repair or decreased damage fixation? , 2005, International journal of radiation biology.

[21]  R. Ray,et al.  Poly (ADP‐ribose) polymerase (PARP) is essential for sulfur mustard‐induced DNA damage repair, but has no role in DNA ligase activation , 2006, Journal of applied toxicology : JAT.

[22]  H. Bernstein,et al.  DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. , 2002, Mutation research.

[23]  Shu-zheng Liu Nonlinear Dose-Response Relationship in the Immune System following Exposure to Ionizing Radiation: Mechanisms and Implications , 2003, Nonlinearity in biology, toxicology, medicine.