Differential gene expression in γ-irradiated BALB/3T3 fibroblasts under the influence of 3-aminobenzamide, an inhibitior of parp enzyme

被引：11
作者：
Cardoso, RS
Espanhol, AR
Passos, GAS
Sakamoto-Hojo, ET
机构：
[1] USP, Dept Biol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, Brazil
[2] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Disciplina Genet, DMEF, BR-14049 Ribeirao Preto, Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Grp Imunogenet Mol, BR-14049 Ribeirao Preto, Brazil
来源：
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS | 2002年 / 508卷 / 1-2期
基金：
巴西圣保罗研究基金会;
关键词：
3-aminobenzamide; poly(ADP-ribose) polymerase; ionizing radiation; gene expression; cDNA macroarrays;
D O I：
10.1016/S0027-5107(02)00141-0
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
3-Aminobenzamide (3AB) is an inhibitor of poly (ADP-ribose) polymerase (PARP), an enzyme implicated in the maintenance of genomic integrity, which is activated in response to radiation-induced DNA strand breaks. cDNA macroarray membranes containing 1536 clones were used to characterize the gene expression profiles displayed by mouse BALB/3T3 fibroblasts (A31 cell line) in response to ionizing irradiation alone or in combination with 3AB. A31 cells in exponential growth were pre-treated with 3AB 4 mM 1 h before gamma-irradiation (4 Gy), remaining in culture during 6 h until harvesting time. A31 cells treated with 3AB alone presented a down-regulation in genes involved in protein processing and cell cycle control, while an up-regulation of genes involved in apoptosis and related to DNA/RNA synthesis and repair was verified. A31 cells irradiated with 4 Gy displayed 41 genes differentially expressed, being detected a down-regulation of genes involved in protein processing and apoptosis, and genes controlling the cell cycle. Concomitantly, another set of genes for protein processing and related to DNA/RNA synthesis and repair were found to be up-regulated. A positive or negative interaction effect between 3AB and radiation was verified for 29 known genes. While the combined treatment induced a synergistic effect on the expression of LCK proto-oncogene and several genes related to protein synthesis/processing, a negative interaction effect was found for the expression of genes related to cytoskeleton and extracellular matrix assembly (SATB1 and Anexin III), cell cycle control (tyrosine kinase), and genes participating in DNA/RNA synthesis and repair (RNA helicase, FLAP endonuclease-1, DNA-3 glycosylase methyladenine, splicing factor SC35 and Soh 1). The present data open the possibility to investigate the direct participation of specific genes, or gene products acting in concert in the mechanism underlying the cell response to radiation-induced DNA damage under the influence of PARP inhibitor. (C) 2002 Elsevier Science B.V. All rights reserved.
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收藏
页码：33 / 40
页数：8
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