In vivo covalent binding of aflatoxin B1 and aflatoxin M1 to liver DNA of rat, mouse and pig

Lutz, Werner; Jaggi, W.; Lüthy, Jürg; Sagelsdorff, Peter; Schlatter, Ch.

doi:10.1016/0009-2797(80)90092-7

Cited by 43 publications

(11 citation statements)

References 21 publications

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“…A good correlation between covalent DNA binding and carcinogenic potency could be found for genotoxic carcinogens, i.e., within 1 order of magnitude (Lutz, 1979;Lutz et al, 1980;Garner, 1980). DNA-binding studies allow distinction between strong, intermediate, and low carcinogenic activity in the target organ under consideration.…”

Section: Discussionmentioning

confidence: 97%

“…The result is expressed in terms of a "covalent binding index" (CBI), which is defined by damage dose pmol of substance bound/pmol of DNA nucleotide mmol of substance applied/kg of animal CBI = -If mixtures of different, even unknown, radiolabeled compounds are to be assessed for DNA-binding activity, the CBI of the mixture is defined as radioactivity bound/pmol of DNA nucleotide radioactivity applied/kg of animal CBI = Measuring the CBI of mixtures has the advantage that any synergistic effects are expressed in the result. An example for determining the CBI of a mixture has been published by Jaggi et al (1980).…”

Section: Discussionmentioning

confidence: 99%

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Ammoniation of aflatoxin-containing corn: distribution, in vivo covalent deoxyribonucleic acid binding, and mutagenicity of reaction products

Schroeder¹,

Zweifel²,

Sagelsdorff³

et al. 1985

J. Agric. Food Chem.

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3H]Aflatoxin B1 (AF ' B,) was ammoniated at 100 OC and the isolated aflatoxin D1 (AFD,) characterized by 'H NMR and mass spectrometry. AFDl was found to be 130-fold less mutagenic than AFB, in the Ames test. In vivo covalent binding to rat liver DNA expressed in the units of a covalent binding index (CBI, a quantitative indicator for genotoxicity) of [14C]AFDl was below the detection limit of 71 and at least 280-times lower than for AFB1, although AFD, still has the 8,9a double bond. After ammoniation of [14C]AFB1-spiked corn grits for 34 days (18.8% H20/2.02% NH3, 25 "C), 14C distribution and CBI were measured: 7% of the radioactivity was CH2C12 extractable but 14% was extractable when acidified prior to extraction. The H 2 0 phase contained 42% 14C with a CBI of 1000 but only 31% 14C with a CBI of below the detection limit of 145 when acidified prior to extraction. The extracted corn had still a radioactivity of 33% (38% respectively) with a CBI of <126. More than 85% of the H20 fraction pass a dialpis membrane with an exclusion limit of 14 OOO dalt~ns. The results indicate that ammoniation reduces the genotoxicity of AFB,-containing corn at least 20 times. Besides unreacted AFBl the aqueous phase contained about 7% of a still toxic AFBl hydrolysis product, which can rebuild AFBl after acidification.Numerous attempts have been made to detoxify by chemical means natural goods contaminated with aflatoxins (Codifer et al.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Ammoniation of aflatoxin-containing corn: distribution, in vivo covalent deoxyribonucleic acid binding, and mutagenicity of reaction products

Schroeder¹,

Zweifel²,

Sagelsdorff³

et al. 1985

J. Agric. Food Chem.

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“…Covalent binding of aflatoxin B 1 to liver DNA of various animal species has been shown to reflect their susceptibility for liver tumor formation (Lutz et al 1980). Since non-immunized rabbits gave rise to a CBI of almost 10,000 they could be about as susceptible as rats for which CBI of 10,000 has been reported (Lutz et L' ' ' 252 M. Caviezel et al al.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Covalent Binding of Aflatoxin B1 to Rabbit Liver DNA After Immunization Against this Carcinogen

Caviezel

Aeschbach

Lutz

et al. 1984

Archives of Toxicology

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Abstract. The covalent binding of [ 3 H]aflatoxin B 1 (AF) to liver DNA was determined, 6 h after oral administration to male rabbits. A Covalent Binding Index, CBI (flmol AF/mol DNA-P)/(mmol AF/kg b. w.) = 8,500was found. Pretreatment of rabbits with AF coupled to bovine serum albumin in Freund's adjuvant led to the production of AF-directed antibodies. Administration of [ 3 H]AF to such immunized rabbits resulted in a CJH of only 2,500, i.e., the iiDJ{.lUnization provided a protection by a factor of more than 3. Although this is encouraging evidence for the potential of active immunization against genotoxic carcinogens, a nurober of pointswill have to be clarified, such as the time course for the DNA binding and the question of a possible shift to other target cells.

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“…The values measured so far span about five orders of magnitude, ranging from more than 10 4 [aflatoxin 8 1 (Lutz et a/., 1980)] down to about one [e.g. benzene (Lutz and Schlatter, 1977b)].…”

Section: The Cova/ent Binding Indexmentioning

confidence: 99%

Investigation of the potential for binding of di(2-ethylhexyl) phthalate (DEHP) and di(2-ethylhexyl) adipate (DEHA) to liver DNA in vivo

Däniken

Lutz

Jäckh

et al. 1984

Toxicology and Applied Pharmacology

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. (1984). Toxico/. App/. Pharmaco/. 73,[373][374][375][376][377][378][379][380][381][382][383][384][385][386][387]. It was the aim oftbis investigation to determine whether covalent binding of di(2.ethylhexyl) phthalate (DEHP) to rat liver DNA and of di(2-ethylhexyl) a(iipate (DEHA) to mouse liver DNA could be a mechanism of action contributing to the observed induction of liver tumors after lifetime feeding of the respective rodent species with high doses of DEHP and DEHA. For this purpose, DEHP and DEHA radiolabeled in different parts of the molecule were administered orally to female rats and mice, respectively, with or witbout pretreatment for 4 weeks with 1% unlabeled compound in the diet. Liver DNA was isolated after 16 hr and analyzed for radioactivity. The data were converted to a covalent binding index, CBI = (micromoles of substance bound per mole of DNA nucleotides)/(millimoles of substance applied per kilogram body weight), in order to allow a quantitative comparison also with other carcinogens and noncarcinogens. Administration of C]hexanol perfonned with both rats and mice allowed the conclusion tbat most if not all DEHA radioactivity in mouse liver DNA was due to biosynthetic incorporation. A maximum possible true DNA binding by DEHA must be below CBI 0.01. Pretreatment of the animals witb unlabeled compound bad no effect on the DNA radioactivities in either species. The present negative data, in conjunction witb other negative short-term tests for mutagenicity, strongly indicate that covalent interaction with DNA is highly unlikely to be the mode of tumorigenic action of DEHP and DEHA in rodents.The plasticizer di(2-ethylhexyl) phthalate (DEHP) was reported to induce liver tumors in F344 rats and B6C3Fl mice in a 2-year

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In vivo covalent binding of aflatoxin B1 and aflatoxin M1 to liver DNA of rat, mouse and pig

Cited by 43 publications

References 21 publications

Ammoniation of aflatoxin-containing corn: distribution, in vivo covalent deoxyribonucleic acid binding, and mutagenicity of reaction products

Ammoniation of aflatoxin-containing corn: distribution, in vivo covalent deoxyribonucleic acid binding, and mutagenicity of reaction products

Reduction of Covalent Binding of Aflatoxin B1 to Rabbit Liver DNA After Immunization Against this Carcinogen

Investigation of the potential for binding of di(2-ethylhexyl) phthalate (DEHP) and di(2-ethylhexyl) adipate (DEHA) to liver DNA in vivo

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