Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis.
OBJECTIVE
Dietary aflatoxin B(1) (AFB(1)) exposure and iron overload are important causes of hepatocellular carcinoma in sub-Saharan Africa. The aim of this study was to investigate if the two risk factors have an interactive effect.


METHODS
Four groups of Wistar albino rats were studied for 12 months. Group 1 (control) was fed the normal chow diet; group 2 (Fe) was supplemented with 0.75% ferrocene iron; group 3 (Fe+AFB(1)) was fed 0.75% ferrocene throughout and gavaged 25 microg AFB(1) for 10 days; group 4 (AFB(1)) was gavaged 25 microg AFB(1) for 10 days. Iron profile, lipid peroxidation (LPO), 8-hydroxydeoxyguanosine (8OHdG), oxidative lipid/DNA damage immunohistochemistry, superoxide/nitrite free radicals, cytokines IL6, IL-10, transaminases (ALT/AST) and Ames mutagenesis tests were performed.


RESULTS
LPO and ALT showed a significant (p<0.05)/additive effect and 8OHdG a significant (p<0.05)/multiplicative effect in the Fe+AFB(1) group. IL-6 produced a negative synergy as against an additive antagonistic effect with IL-10. Massive deposits of 4-hydroxynonenal (4-HNE) and 8OHdG were observed in liver sections of the Fe+AFB(1) group, suggestive of multiplicative synergy. Significant levels of mutagenesis (p<0.001) were observed in the Fe+AFB(1) group. This multiplicative synergy was five-fold.


CONCLUSIONS
Dietary iron overload and AFB(1) have a multiplicative effect on mutagenesis.
Asare
George A
GA
MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Medical School, Parktown 2193, Johannesburg, South Africa.
Bronz
Michelle
M
Naidoo
Vivash
V
Kew
Michael C
MC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016604:Aflatoxin B1 / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D000447:Aldehydes; D016207:Cytokines; D008054:Lipid Peroxides; D009566:Nitrates; D009573:Nitrites; D014168:Transferrin; D013481:Superoxides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D016604:Aflatoxin B1; D007501:Iron; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal