TY - JOUR A1 - Lutz, Werner K. A1 - Jaggi, W. A1 - Lüthy, J. A1 - Sagelsdorff, P. A1 - Schlatter, C. T1 - In vivo covalent binding of aflatoxin B\(_1\) and aflatoxin M\(_1\) to liver DNA of rat, mouse and pig N2 - [\(^{14}\)C] Aflatoxin B\(_1\) (AFB\(_1\)) was isolated from cultures of Aspergillus parasiticus grown on [1-\(^{114}\)C] sodium acetate. Covalent binding of AFB1 to liver DNA of rat and mouse was determined 6-8 h afteroral administration. The effectiveness of covalent binding, expressedas DNA binding per dose in the units of a 'Covalent Binding Index' (CBI), (\(\mu\)mol aflatoxin/mol DNA nucleotides)/(mmol aflatoxin/kg animal), was found to be 10 400 for rats and 240 for mice. These CBI partly explain the different susceptibility of the two species for the incidence of hepatic tumors. The corresponding values for pig liver DN A, 24 and 48 h after oral administration, were found to be as high as 19 100 and 13 300. DNA-binding has not so far been reported for this species although it could represent an appropriate animal model for studies where a human-like gastrointestinal tract physiology is desirable. Aflatoxin M \(_1\) ( AFM\(_1\)) is a metabolite found in the milk of cows that have been fed AFB\(_1\)-contaminated diet. [\(^{14}\)C] AFM\(_1\) was also found to be produced by cultures of A. parasiticus giving a yield of about 0.3% of the total aflatoxins. A test for covalent binding to rat liver DN A revealed a CBI of 2100 shoWing that AFM\(_1\) must also be regarded as a strong hepatocarcinogen. It is concluded that AFB\(_1\) contaminations should be avoided in dairy feed. KW - Toxikologie Y1 - 1980 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61097 ER - TY - JOUR A1 - Jaggi, W. A1 - Lutz, Werner K. A1 - Lüthy, J. A1 - Zweifel, U. A1 - Schlatter, C. T1 - In vivo covalent binding of aflatoxin metabolites isolated from animal tissue to rat-liver DNA N2 - Ring-labelled [\(^{14}\)C)aflatoxin B\(_1\) (AFB\(_1\)), prepared by biosynthesis. or generally labelled [\(^3\)H]AFB\(_1\) was administered by oral gavage to young adult male rats. After 6 hr. the liver was removed and two fractions were isolated, namely macromolecules, which contamed about 3 % of the initial dose of AFB\(_1\) radioactivity. and water-soluble, low-molecular aftatoxin conjugates containing about0·2% of the administered radioactivity. These two fractions were administered orally to other rats in order to determine the potential of radioactive aftatoxin residues for covalent binding to DNA. Such binding can be used as an indicator for carcinogenic potency. Liver DNA was isolated 9-12 hr after admmistration of the aflatoxin derivatives and in no case was any radioactivity detected on the DNA. It can be deduced on the basis of the limit of detection of radioactivity on the DNA, that macromolecule bound AFB\(_1\) derivatives are at least 4000 times less active than AFB\(_1\) with respect to covalent binding to rat-liver DNA. and that the water-soluble conjugates are at least 100 times less potent than AFB, itself. It is concluded that the carcinogenic risk for humans who consume liver or meat. containing such aflatoxin residues is negligible when compared with the risk from intake of aftatoxins in other food items. KW - Toxikologie Y1 - 1980 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61101 ER -