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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2012.tde-01082012-083600
Document
Author
Full name
Iana Suly Santos Katz
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Ribeiro Filho, Orlando Garcia (President)
Campa, Ana
Kaneno, Ramon
Lima, Wothan Tavares de
Mauro, Eliana Faquim de Lima
Title in Portuguese
Mielotoxicidade por 7,12-dimetilbenzantraceno e sua repercurssão na resposta imunológica dos camundongos AIRmax e AIRmin.
Keywords in Portuguese
Camundongos
Ciclo celular
Medula óssea de animal
Neutrófilos
Toxicidade em animal
Abstract in Portuguese
Estudamos nos camundongos geneticamente selecionados para alta (AIRmax) ou baixa (AIRmin) resposta inflamatória aguda os efeitos tóxicos do DMBA na medula óssea e sua repercussão na resposta imunológica após 24 horas. O tratamento diminuiu a produção de IgG anti-HGG e a migração celular para o tecido subcutâneo após injeção sc com Biogel nos AIRmin, como também causou hipocelularidade, principalmente de neutrófilos maduros. Contudo, houve um aumento de blastos e neutrófilos imaturos. A análise do ciclo celular em células Lin- revelou bloqueio da fase S nos AIRmin tratados com DMBA. A cinética de dano no DNA mostrou que o reparo no DNA é mais rápido em AIRmax. Os níveis de expressão do gene parp-1 triplicou em AIRmax, enquanto que nos AIRmin aumentou p53 e caspase-3. Os AIRmin tratados com DMBA apresentam perda da capacidade proliferativa e de diferenciação quando estimuladas in vitro com fatores hematopoéticos. O DMBA causou mielotoxicidade nos AIRmin, podendo afetar o desenvolvimento da resposta imune, enquanto AIRmax foram resistentes a esses efeitos.
Title in English
Myelotoxicity by 7,12-Dimetilbenzantraceno and its impact on immune response in AIRmax and AIRmin mice.
Keywords in English
Bone marrow from animal
Cell cycle
Mice
Neutrophils
Toxicity animal
Abstract in English
We investigated in mice genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory response the toxic effects of DMBA treatment on the BM and its impact on the immune response. DMBA treatment diminished specific IgG anti-HGG production and the cellular migration to the inflammatory site after sc injection of biogel in AIRmin, and hypocellularity in BM, mostly in the neutrophil. However we observed an increase of immature cells. Cell cycle analysis of Lin cells showed a decrease of cells in S stage from DMBA-treated AIRmin mice. The kinetics of cell repair demonstrated the early removal of DNA lesion from DMBA-treated AIRmax mice. The parp-1 gene showed 3 fold increased mRNA expression in AIRmax cells, however in AIRmin mice there was an increase in p53 and caspase-3 mRNA mRNA expression. Myeloid cells from DMBA treated AIRmin mice showed low differentiation and proliferation capacities after in vitro hematopoietic factors. DMBA treatment produced myelotoxicity in AIRmin mice, affecting immune response development, but AIRmax mice were resistant.
 
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Publishing Date
2012-08-15
 
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