Gene expression profiles in human cells submitted to genotoxic stress

Autor(es)

Sakamoto-Hojo, E. T. ^[1] ; Pereira, E. ; Fachin, A. L. ; Cardoso, R. S. ; Donadi, E. A. ; Passos, G. A. S. ; Mello, S. S. ; Junta, C. M.

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto - Brasil

• Tipo de documento: Artigo Científico
• Fonte: MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH; v. 544, n. 2-3, p. 403-413, Nov. 2003.
• Área do conhecimento: Ciências Biológicas - Genética
• Assunto(s): Expressão gênica Radiação ionizante

Resumo

Cell response to genotoxic agents is complex and involves the participation of different classes of genes (DNA repair, cell cycle control, signal transduction, apoptosis and oncogenesis). In this report, we present three approaches to document gene expression profiles, dealing with the evaluation of cellular responses to genotoxic agents (gamma-rays from 60Cobalt and cyclophosphamide). We used the method of cDNA arrays to analyze the differential gene expression profiles that were displayed by lymphocytes from radiation-exposed individuals, a human fibroblast cell line, and T lymphocytes from systemic lupus erythematosus (SLE) patients who were treated with cyclophosphamide. A preliminary analysis performed in lymphocytes from three radiation-workers showed that several induced genes can be associated with cell response to ionizing radiation: TRRAP (cell cycle regulation), Ligase IV (DNA repair), MAPK8IP1 and MAPK10 (signal transduction), RASSF2 (apoptosis induction/tumorigenesis), p53 (damage response/maintenance of genetic stability). The in vitro irradiated normal VH16 cell line (primary) showed a complex response to the genotoxic stress at the molecular level. Many apoptotic pathways were concomitantly induced. In addition, several genes involved in signaling and cell cycle arrest/control were significantly modulated after irradiation. Many genes involved in oxidative damage were also induced, indicating that this mechanism seems to be an important component of cell response. After treatment of the SLE patients with cyclophosphamide, 154 genes were differentially and significantly induced. Among them, we identified those associated with drug detoxification, cell cycle control, apoptosis, and tumor-suppressor. These findings indicate that at least two apoptotic pathways were induced after cyclophosphamide treatment. The induction of APAF1 and two genes coding for two subunits of cytochrome c supports a previous report showing increased apoptosis in lymphocytes from SLE patients. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research. (AU)

• Processo FAPESP: 02/01441-6 - Expressão gênica diferencial em larga escala em pacientes com Lúpus Eritematoso Sistêmico
• Beneficiário: Paula Sandrin Garcia
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
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• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 01/10995-2 - Expressão gênica diferencial induzida pela radiação ionizante analisada por micro arrays em linfócitos humanos
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• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 00/09063-5 - Expressão gênica diferencial em larga escala em pacientes com Lúpus Eritematoso Sistêmico
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• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 00/01005-6 - Análise da expressão de genes reguladores do ciclo celular e do gene TCR híbrido (cromossomo 7) induzida pela radiação ionizante em fibroblastos humanos
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• Modalidade de apoio: Bolsas no Brasil - Mestrado