METABOLISM OF 2,4-DINITRO[C-14]TOLUENE BY FRESHLY ISOLATED FISCHER-344 RAT PRIMARY HEPATOCYTES

Google Scholar
  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (1) , 10-14
Abstract
Fischer-344 rat hepatocytes display a capacity for oxidation and reduction of 2,4-dinitrotoluene (2,4-DNT), a potent hepatocarcinogen. The major metabolite detected by high-pressure liquid chromatography was 2,4-dinitrobenzyl alcohol (2,4-DNBalc), which accounted for 75-80% of the total metabolites. The apparent Km and Vmax for 2,4-DNBalc formation was 58.0 .mu.M and 25.5 nmol/106 cells/30 min, respectively. Formation of 2,4-DNBalc was enhanced by treatment of rats with Aroclor 1254 (6-fold), phenobarbital (3.5-fold) and 3-methylcholanthrene (3.5-fold). In vitro additions of SKF 525-A or 7,8-benzoflavone inhibited the formation of 2,4-DNBalc. Hepatocytes incubated under decreased oxygen concentrations (15, 10 or 5% O2 in N2) displayed higher levels of reductive metabolism of 2,4-DNT (up to 5-fold) than when incubated in air. Concomitant decreases in oxidative metabolism of 2,4-DNT were observed in these experiments. Hepatocyte metabolism of 2-amino-4-nitrotoluene and 4-amino-2-nitrotoluene, 2 major products of rat cecal metabolism of 2,4-DNT, to 2-(N-acetyl)amino-4-nitrotoluene and 4-(N-acetyl)amino-2-nitrotoluene, respectively, was observed. Hepatic reductive metabolism of 2,4-DNT probably plays a minor role in the overall metabolic scheme of 2,4-DNT.