Malaria infection modulates effects of genotoxic chemicals in the mouse bone-marrow micronucleus test

• Published in: Mutation research Vol. 649; no. 1; pp. 28 - 33
• Main Authors: Poça, Kátia S., De-Oliveira, Ana C.A.X., Santos, Manoel J.S., Paumgartten, Francisco J.R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08-01-2008; Elsevier
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Animals; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - metabolism; Carcinogenicity; Carcinogens - toxicity; Cyclophosphamide - toxicity; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP2B1 - metabolism; Cytochrome-P450; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Human protozoal diseases; Infections; Infectious diseases; Malaria; Malaria - blood; Malaria - parasitology; Malaria - physiopathology; Medical sciences; Mice; Mice, Inbred C57BL; Micronucleus Tests - methods; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Mutagenicity; Parasitic diseases; Plasmodium berghei; Protozoal diseases; Toxicology; Xenobiotic biotransformation; Cytochrome-P450; Plasmodium berghei; Infections; Mutagenicity; Xenobiotic biotransformation; Carcinogenicity; Protozoal disease; Micronucleus test; Malaria; Toxicity; Mutagenicity testing; Cytochrome P450; Rodentia; Genotoxicity; Parasitosis; Infection; Vertebrata; Toxicology; Mammalia; Mouse; Bone marrow; Genetics; Xenobiotic
• ISSN: 1383-5718; 0027-5107; 1879-3592
• DOI: 10.1016/j.mrgentox.2007.07.006

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, 50
mg/kg body weight) or ethyl methanesulfonate (EMS, 150
mg/kg body weight), on post-infection days 9–12 when parasitemia was ≥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.