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Mutagenesis Advance Access published online on June 14, 2005
Mutagenesis, doi:10.1093/mutage/gei034
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© The Author 2005. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received July 15, 2004
Revised March 30, 2005
Accepted April 15, 2005

Original article

Influence of orange juice over the genotoxicity induced by alkylating agents: an in vivo analysis

Silvia Isabel Rech Franke 1, Daniel Prá 2, Bernardo Erdtmann 3, João Antonio Pêgas Henriques 4, and Juliana da Silva 5*

1 Curso de Nutrição, Departamento de Educação Física e Saúde, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS, Brazil; Genotox/Centro de Biotecnologia/Programa de Pós-Graduação em Biologia Celular e Molecular/Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, R S, Brazil
2 Genotox/Centro de Biotecnologia/Programa de Pós-Graduação em Biologia Celular e Molecular/Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, R S, Brazil
3 Genotox/Centro de Biotecnologia/Programa de Pós-Graduação em Biologia Celular e Molecular/Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, R S, Brazil; Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil
4 Genotox/Centro de Biotecnologia/Programa de Pós-Graduação em Biologia Celular e Molecular/Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, R S, Brazil; Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil; Curso de Biologia/Curso de Farmácia, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil
5 Genotox/Centro de Biotecnologia/Programa de Pós-Graduação em Biologia Celular e Molecular/Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, R S, Brazil; Curso de Biologia/Curso de Farmácia, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil

* To whom correspondence should be addressed.
Juliana da Silva, E-mail: juliana.silva{at}ulbra.br


  Abstract

There is considerable epidemiological evidence indicating an association between diets rich in fresh fruit and vegetables and a decreased incidence of cancers. Methyl methanesulfonate (MMS) and cyclophosphamide (CP) are alkylating agents that differ in their mode of action. MMS is a directly-acting, monofunctional agent, while CP is a bifunctional agent that requires metabolic activation to a reactive metabolite. To evaluate if orange juice could reduce DNA damage induced by these alkylating agents, mice were treated orally (by gavage) with MMS and CP, prior to and after treatment with orange juice. DNA damage was evaluated by the comet assay in peripheral white blood cells. Under these experimental conditions, orange juice reduced the extent of DNA damage caused by both mutagens. For MMS, the antigenotoxic effect of the orange juice was both protective (orange juice pre-treatment) and reparative (orange juice post-treatment); for CP, the effect was reparative only. The components of orange juice can have several biological effects, including acting as targets of toxicants and modulating metabolization/detoxification routes. Considering the different mechanisms of the action of the two drugs, different protective effects are suggested. These results demonstated the ability of the in vivo comet assay to detect in vivo modulation of MMS and CP mutagenicity by orange juice.


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