Investigation of covalent aflatoxin B1-DNA adducts formed in vivo in rainbow trout (Salmo gairdneri) embryos and liver.
The formation of covalent aflatoxin-DNA adducts has been studied in embryo and yearling stages of the rainbow trout (Salmo gairdneri). A linear relationship was found between the amount of aflatoxin B1 (AFB1) absorbed into 21-day-old eggs and the level of covalent modification of embryo DNA after exposure to 0.25 to 0.5 p.p.m. aqueous solutions of AFB1 for 1 h; higher concentrations resulted in absorption of a greater proportion of AFB1. The principal covalent product, identified after acid and enzymatic hydrolysis of isolated embryo DNA, was chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxy aflatoxin B1. Additional AFB1 derivatives which were present are believed to be formed by chemical transformation of this product in DNA producing an aflatoxin-formamidopyrimidine adduct and the metabolic activation of other aflatoxin metabolites, such as aflatoxin M1 and aflatoxin P1. Although the eggs were exposed to AFB1 for a short time, covalent modification of DNA was evident over an extended period. The highest level of covalent products was present at approximately 24 h after exposure to 0.5 p.p.m. AFB1. Ninety-six hours later, this level had decreased slightly; however, the distribution of covalent adducts had changed: formamidopyrimidine adducts now represented up to 50% of the hydrolyzed aflatoxin derivatives. A similar pattern of covalent aflatoxin derivatives was found in the liver DNA of yearling trout 10 h after the administration of 0.3 mg/kg AFB1.
Croy
R G
RG
Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nixon
J E
JE
Sinnhuber
R O
RO
Wogan
G N
GN
D000042:Absorption; D016604:Aflatoxin B1 / Q000096:biosynthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D002845:Chromatography; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D017686:Oncorhynchus mykiss; D014316:Tritium
D018736:DNA Adducts; C072611:aflatoxin B1-DNA adduct; D014316:Tritium; D004247:DNA; D016604:Aflatoxin B1