Binding of dibenzo(a,e)fluoranthene, a carcinogenic, polycyclic hydrocarbon without K-region, to nucleic acids in a subcellular microsomal system.
Dibenzo(a,e)fluoranthene (DBF), a highly carcinogenic polycyclic hydrocarbon without an apparent K-region, binds covalently to DNA, transfer RNA, and polyribonucleotides when incubated with hepatic microsomal fractions under standard conditions. Optimal binding conditions for [3H]DBF were established. Methylcholanthrene-pretreated mouse liver microsomes induced a higher level of binding of [3H]DBF to DNA than did similarly induced rat liver microsomes. 7,8-Benzoflavone strongly inhibited the binding of this polycyclic aromatic hydrocarbon to DNA, while cyclohexene oxide and trichloropropene oxide had an enhancing effect when used in the presence of rat liver microsomes. An unexpected inhibitory effect was observed with cyclohexene oxide in mouse liver microsome-enriched medium. [3H]DBF bound twice as much to denatured as to native DNA. Incubation of [3H]DBF in the presence of liver microsomes and polyribonucleotides (polyadenylate, polyuridylate, polyguanylate, and polyinosinate) indicated that binding occurs mainly with guanine. Binding of [3H]DBF to DNA of various origins was found to be directly proportional to the amount of GC pairs. Preliminary results indicate a covalent bond between DBF and nucleic acids.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D053138:Cyclohexenes; D004247:DNA / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D005449:Fluorenes / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009691:Nucleic Acid Denaturation; D011119:Polynucleotides / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D051381:Rats
D001571:Benzoflavones; D003510:Cyclohexanes; D053138:Cyclohexenes; D004852:Epoxy Compounds; D005449:Fluorenes; D006843:Hydrocarbons, Chlorinated; D011119:Polynucleotides; C007193:cyclohexene oxide; D008748:Methylcholanthrene; D004247:DNA; D012343:RNA, Transfer