Micronuclei, chromosomal aberrations and aflatoxin-albumin adducts in experimental animals after exposure to aflatoxin B1.
Rats and mice differ markedly in sensitivity to aflatoxin B1 (AFB1) hepatocarcinogenicity, the former being sensitive and the latter resistant. Animals were treated with single doses of different concentrations of AFB1, between 0.01 and 1.0 microgram AFB1/g body weight. The frequency of chromosomal aberrations and micronuclei in the bone marrow was measured and compared to the level of AFB1 bound covalently to albumin in the peripheral blood. Both chromosomal aberrations and micronuclei were significantly increased in treated rats compared to the control group at doses above 0.1 microgram/g. In contrast, in mice, a slight increase in chromosome aberrations was seen in the highest dose group (1.0 microgram/g) but no increase in micronuclei was observed at any of the doses. The level of chromosomal aberrations was about 10 times higher in rats than in mice at the highest dose of AFB1. AFB1-albumin (AF-alb) adducts did not show a strong dose-response increase after treatment in mice, whereas in rats the levels increased linearly with dose of AFB1 and there were strong correlations at the individual rat level with both chromosomal aberrations (r = 0.92; p < 0.0001) and micronucleus frequency (r = 0.86; p < 0.0001). These data suggest that the AF-alb may reflect the level of genetic alteration resulting from the initial binding of this carcinogen to cellular DNA. Therefore, this adduct used as a biomarker in studies of human exposure to aflatoxin may provide information not only on exposure but also on the risk of genetic alterations consequent to that exposure.
Anwar
W A
WA
Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt.
Khalil
M M
MM
Wild
C P
CP
D016604:Aflatoxin B1 / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002869:Chromosome Aberrations; D004247:DNA; D018736:DNA Adducts; D004249:DNA Damage; D006801:Humans; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D018736:DNA Adducts; D009153:Mutagens; C072611:aflatoxin B1-DNA adduct; D004247:DNA; D016604:Aflatoxin B1