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Microsome-dependent Binding of Benzo(a)pyrene and Aflatoxin B₁ to DNA, and Benzo(a)pyrene Binding to Aflatoxin-conjugated DNA¹

Institut de Recherches Scientifiques sur le Cancer, Boîte Postale 8, 94800 Villejuif, France

Aflatoxin B₁-conjugated DNA and benzo(a)pyrene (BP)-conjugated DNA (the DNA complexes formed with the active forms of these carcinogens) were isolated after incubation in vitro with liver microsomes from control, phenobarbital, methylcholanthrene, and phenobarbital plus methycholanthrene-treated rats and the reduced nicotinamide adenine dinucleotide phosphate-generating system. A DNA complex containing both carcinogens was then obtained by subsequent fixation of BP to the aflatoxin B₁-conjugated DNA. Aryl hydrocarbon hydroxylase, which had levels of activity that varied with the different microsomal systems, was found to be highly specific in the activation of the two carcinogens to forms that bind to DNA. Depending on the microsomal system, BP binding to DNA increased from 2 to 6 times, but increased only 2 times for aflatoxin binding to DNA. 7,8-Benzoflavone caused an 80% inhibition of BP binding to DNA with methylcholanthrene microsomes and phenobarbital plus methylcholanthrene microsomes, but only 20 and 0%, respectively, with aflatoxin B₁. However, with control and phenobarbital microsomes, a 30 to 50% increase in the binding level of aflatoxin B₁ to DNA was obtained, while with BP the binding decreased 32% with these microsomes.

The fixation of ethyl acetate-soluble metabolites of BP was inhibited up to 70% with the aflatoxin B₁- and aflatoxin G₁-conjugated DNA's, but not with DNA's conjugated with aflatoxin B₂, B_2a, G₂, and M₁. The inhibitory effect on the binding of these metabolites was no longer observed after treatment of the aflatoxin B₁- and aflatoxin G₁-conjugated DNA's with CHCl₃. The in vitro studies on the binding of aflatoxin and BP to DNA by these methods do not give evidence of common binding sites on the DNA molecule for the two carcinogens.

¹ This work was supported in part by the Service d'Exploitation Industrielle des Tabacs et Allumettes (S.E.I.T.A.), Paris, France.

Received 2/11/74. Accepted 7/ 8/74.