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.