Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo.
We have studied the activation of 2,4-diaminoanisole (2,4-DAA), a mutagenic hair-dye component, and 2,4-diaminotoluene (2,4-DAT), a hepatocarcinogen, to products which blind covalently to tissue macromolecules. Four hours after a dose of 100 mg/kg ring-labeled 3H-2,4-DAA, 0.30 nmol is found covalently bound per mg liver protein. This amount is increased by 83% after phenobarbital pretreatment, and by 43% after beta-naphthoflavone-pretreatment. Almost the same degree of binding is seen in kidneys. Subcellular fractionation of livers shows that most of the bound material is in the microsomal fraction. Similar levels of covalent protein binding is seen after administering ring-labeled 3H-2,4-DAT. No significant binding to DNA in vitro or in vivo could be demonstrated using 3H-2,4-DAA or 3H-2,4-DAT, whereas 3H-2,4-DAT is found to covalently bind to hepatic RNA.
D000818:Animals; D000840:Anisoles / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010655:Phenylenediamines / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D000840:Anisoles; D004396:Coloring Agents; D005419:Flavonoids; D010655:Phenylenediamines; D010634:Phenobarbital