Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo. 27 4

2,4-Dinitrotoluene (2,4-DNT) is an important industrial nitroaromatic compound. 2,4-Diaminotoluene (2,4-DAT), one of the urinary metabolites of 2,4-DNT, is carcinogenic when fed to rats. The objectives of these studies were to determine whether 2,4-DAT was formed from 2,4-DNT in rat liver and to clarify the nature of enzymes responsible for reduction of 2,4-DNT to 2,4-DAT. Data obtained from thin-layer and high-pressure liquid chromatography indicated that metabolites produced by microsomal preparations were 2-amino-4-nitrotoluene (2A4NT) and its isomer (4A2NT). This microsomal activity is probably mediated by cytochrome P-450 because the reduction is blocked by carbon monoxide and primary amines [aniline, n-octylamine, and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA)]. In contrast, 2,4-DNT was metabolized via 2A4NT and 4A2NT to 2,4-DAT by cytosolic preparations. The greatest part of the reduction activity was due to cytosolic xanthine oxidase because the reduction was blocked by allopurinol. The results of this investigation suggest that reduction of 2,4-DNT to 2,4-DAT by cytosolic xanthine oxidase may play a role in 2,4-DNT hepatocarcinogenicity.
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PMID:Reduction of 2,4-dinitrotoluene by Wistar rat liver microsomal and cytosol fractions. 654 24