Malaria infection modulates effects of genotoxic chemicals in the mouse bone-marrow micronucleus test.
Mutat Res
; 649(1-2): 28-33, 2008 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-17851116
Malaria has been reported to modulate the activity of cytochrome-P450 enzymes (CYP). Since CYPs are involved both in the activation and detoxication of xenobiotics, we investigated whether malaria would modify the effects of chemical carcinogens in the bone-marrow micronucleus assay. Female C57BL6 mice were infected with Plasmodium berghei (ANKA) and treated (ip route) with cyclophosphamide (CPA, 25 mg/kg body weight), 7,12-dimethylbenz[a]anthracene (DMBA, 50mg/kg body weight) or ethyl methanesulfonate (EMS, 150 mg/kg body weight), on post-infection days 9-12 when parasitemia was > or =9% of RBC. Controls were age-paired non-infected mice. Bone marrows were sampled at 24 and 48 h (CPA), 24 h (EMS) or 48 h (DMBA) after treatment. The background incidence of polychromatic erythrocytes with micronuclei (MN-PCE) in malaria-infected mice was approximately twofold the background incidence in non-infected controls. Effects of indirect clastogens (CPA and DMBA) in the micronucleus assay were attenuated while the effect of EMS, a direct clastogen, was enhanced by infection. In a separate experiment, malaria was shown to decrease activities of ethoxy-(EROD, a marker for CYP1A) and benzyloxy-(BROD, CYP2B) resorufin-O-dealkylases in liver microsomes. The foregoing findings are consistent with the hypothesis that malaria-caused attenuation of genotoxicity arose from a down modulation of CYP isoforms that convert CPA (CYP2B) and DMBA (CYP1A) into their active metabolites.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium berghei
/
Medula Óssea
/
Carcinógenos
/
Malária
Limite:
Animals
Idioma:
En
Revista:
Mutat Res
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda