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Doctoral Thesis
DOI
10.11606/T.42.2008.tde-15092008-131230
Document
Author
Full name
Simone Gomes Ferreira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Cipolla Neto, Jose (President)
Afeche, Solange Castro
Hyodo, Sandra Aparecida Takahashi
Okazaki, Kayo
Strauss, Eugenia Costanzi
Title in Portuguese
Estudo dos efeitos da melatonina sobre danos ao DNA induzidos pela ciclofosfamida em ratos wistar pinealectomizados.
Keywords in Portuguese
Antineoplásicos
Antioxidantes
Danos do DNA
Glândula pineal
Melatonina
Reparação do DNA
Abstract in Portuguese
Este estudo investigou o efeito protetor da melatonina sobre os danos ao DNA induzidos pela ciclofosfamida (20 e 50mg/kg) sobre as aberrações cromossômicas, fragmentação do DNA, ciclo celular e os sítios sensíveis a Fpg pelo Ensaio Cometa. Os níveis de RNAm de MGMT, p53, p21, Bax, Bcl-2, Top1, CSB e XPF foram analisados por qPCR. Após a remoção cirúrgica da glândula pineal, os animais foram tratados com 1 mg/kg de mel via oral durante 15 dias. Como resultados demonstramos que a melatonina foi capaz de reverter completamente o quadro de aberrações cromossômicas induzidas pela ciclofosfamida, indicando uma possibilidade de uso terapêutico quando da necessidade de uso de medicação quimioterápica. Esse quadro repetiu-se e ficou mais evidente com o estudo específico das lesões oxidativas pelo uso da Fpg. De todos os genes estudados, aquele que teve de forma mais consistente, sua expressão aumentada, sempre, pela melatonina foi XPF. Dessa forma, os mecanismos envolvidos com o reparo do DNA mobilizados pela melatonina parecem, em parte, mobilizar a expressão do gene XPF.
Title in English
Melatonin effects on the DNA damage induced by cyclophosphamide in pinealectomyzed rats.
Keywords in English
Antineoplastic
Antioxidants
DNA damage
DNA repair
Melatonin
Pineal gland
Abstract in English
This study investigated the protetive effect of melatonin over DNA damage-induced by cyclophosphamide (20 and 50mg/kg) characterizing chromosomal aberrations, DNA fragmentation, cell cycle and determination of Fpg-sensitives sites by comet assay. The levels of MGMT, p53, p21, Bax, Bcl-2, Top1, CSB and XPF mRNA were examined by qPCR. After pineal gland surgical removal, animals were treated orally with 1 mg/kg of melatonin during 15 days. Results have shown that melatonin treatment was able to completelly revert chromossomal aberrations cyclophosphamide-induced, posssibly indicating a therapy use of melatonin in chemoterapic treatment. This effect was also demonstrated with the studies of oxidative lesions by Fpg-sensitives assay. From all studied genes, XPF showed the most increased expression. Thereby, DNA repair mechanisms triggered by melatonin, seems to mobilize XPF gene expression.
 
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Publishing Date
2008-10-03
 
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