In vivo aflatoxin B1 metabolism and hepatic DNA adduction in zebrafish (Danio rerio)

• Published in: Toxicology and applied pharmacology Vol. 143; no. 1; pp. 213 - 220
• Main Authors: Troxel, C.M. (Oregon State University, Corvallis.), Reddy, A.P, O'Neal, P.E, Hendricks, J.D, Bailey, G.S
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 01.03.1997
• Subjects: ADN; AFLATOXICOL; AFLATOXICOL-GLUCURONIDE; Aflatoxin B1 - metabolism; Aflatoxin B1 - toxicity; AFLATOXIN B1-8,9-EPOXIDE; AFLATOXINAS; AFLATOXINE; AFLATOXINS; ANIMAL MODELS; Animals; Biological and medical sciences; Biological Assay; BIOLOGICAL DIFFERENCES; Carcinogens - metabolism; Carcinogens - toxicity; DIFERENCIAS BIOLOGICAS; DIFFERENCE BIOLOGIQUE; DNA; DNA Adducts - drug effects; DNA Adducts - metabolism; DNA MODIFICATION; Dose-Response Relationship, Drug; EXCRECION; EXCRETION; Female; FOIE; Food toxicology; HIGADO; Immunity, Innate; INJECTION; INTRAPERITONEAL INJECTION; INYECCION; LIVER; Liver - drug effects; Liver - metabolism; Male; Medical sciences; METABOLISM; METABOLISME; METABOLISMO; METABOLITE; METABOLITES; METABOLITOS; MODELE ANIMAL; MODELOS ANIMALES; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - physiopathology; ONCORHYNCHUS MYKISS; Oncorhynchus mykiss - metabolism; RAINBOW TROUT; SPECIES DIFFERENCES; Species Specificity; TOXICIDAD; TOXICITE; TOXICITY; Toxicology; Zebrafish - metabolism; Digestive system; Interspecific comparison; Liver; Biological transport; Mycotoxin; Metabolism toxicity relation; Sex; Metabolism; In vitro; Mechanism; Resistance; Carcinogen; In vivo; Vertebrata; Animal; DNA; Pisces; Aflatoxin B1; Covalent bond; Models; Oxidation; Kinetics; Molecular adduct
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1996.8058

The zebrafish (Danio rerio) is assuming prominence in developmental genetics research. By comparison, little is known of tumorigenesis and nothing is known of carcinogen metabolism in this species. This study evaluated the ability of zebrafish to metabolize a well-characterized human carcinogen, aflatoxin B1 (AFB1), to phase I and phase II metabolites and assessed hepatic AFB1-DNA adduction in vivo. Fish ip injected with 50-400 micrograms [3H]AFB1/kg body wt displayed a linear dose response for hepatic DNA binding at 24 hr. AFB1-DNA adduct levels among treatments showed no statistical difference over the period from 1 to 21 days after injection, suggesting poor adduct repair in this species. DNA binding in female fish was 1.7-fold higher than that in males (p 0.01). An in vitro AFB1 metabolism assay verified that zebrafish liver extracts oxidize AFB1 to the 8,9-epoxide proximate electrophile (Km