DNA damage-related gene expression as biomarkers to assess cellular response after gamma irradiation of a human lymphoblastoid cell line

• Published in: Oncogene Vol. 19; no. 7; pp. 916 - 923
• Main Authors: BISHAY, K, ORY, K, LEBEAU, J, LEVALOIS, C, OLIVIER, M.-F, CHEVILLARD, S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 17.02.2000; Nature Publishing Group
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Bcl-2 protein; Biological and medical sciences; Biomarkers; Biomarkers - analysis; Cell Count - drug effects; Cell Count - radiation effects; Cell cycle; Cell Cycle - drug effects; Cell Cycle - radiation effects; Cell death; Cell Death - drug effects; Cell Death - radiation effects; Cell Line, Transformed; Cell Nucleus - drug effects; Cell Nucleus - radiation effects; Cell physiology; Cell survival; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cyclin-dependent kinase inhibitor p21; Cytochalasin B - pharmacology; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - radiation effects; DNA repair; Fundamental and applied biological sciences. Psychology; Gamma Rays; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; Humans; Kinases; Lymphocytes - radiation effects; Micronuclei; Micronucleus Tests; Molecular and cellular biology; Molecular modelling; p53 Protein; Proliferating cell nuclear antigen; Proteins; Radiation; Tumor Cells, Cultured; γ Radiation; Human; Radiosensitivity; Micronucleus test; Gene expression; Survival; Gamma irradiation; Cell line; Gene; DNA; Cell cycle; Lesion; Repair; Lymphoblastoid cell; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203405

Since defects in molecular mechanisms controlling DNA repair, cell cycle checkpoint and apoptosis could modify cellular sensitivity to DNA damaging agents, we have conducted a multiparametric molecular analysis for better understanding the regulation pathways leading to cell survival or cell death after irradiation. Using a human lymphoblastoid cell line, we have analysed, following gamma irradiation (0.5, 1, 2, 4, 8, 16 and 32 Gy, at 0.5, 24, 48 and 72 h after treatment), the correlation between proliferation, cell cycle analysis, apoptosis and micronuclei frequency with the expression of TP53, WAF1, DNA LIGASE 1, PCNA, BAX, BLC-2, BAK, DAD1, ICH1-Long and -Short forms mRNAs. We have found that whereas TP53, BAK, ICH1-Short form, and DAD1 were expressed at constant levels, WAF1, PCNA, BAX were up-regulated, ICH1-Long form, DNA LIGASE 1, and BCL-2 were down-regulated. These modifications of expression were significantly correlated with doses, survival, proliferation, cell cycle delays, and apoptosis. A positive correlation of WAF1 and BAX, and a borderline negative correlation with BCL-2 expressions were observed with micronuclei frequency for doses ranging from 0.5 to 4 Gy. In conclusion, our data clearly demonstrate that gene expression profiling, which is easier and more rapid to conduct than the assessments of classical phenotypic responses, could be useful to improve knowledge concerning pathways involved in cellular response to irradiation, knowing that such biomarkers could constitute tools to assess radio-sensitivity/radio-resistance. Oncogene (2000) 19, 916 - 923.