Nitroreduction of 2,4-dinitrotoluene in vitro by cytochrome P-450 induced H4IIE cells.
Conditions have been established for H4IIE rat hepatoma cell cultures in which effects of cytochrome P-450 induction on the metabolism of a munitions wastestream pollutant can be studied. Under these conditions, the polychlorinated hydrocarbon 2,3,4,7,8-pentachlorodibenzfuran (PCDBF) induced cytochrome P-450 (1A1) aryl hydrocarbon hydroxylase (AHH) activity over a wide range of concentrations without significant cytotoxic effects. The munition pollutant 2,4-dinitrotoluene (2,4-DNT) did not induce AHH activity itself, but its metabolism was considerably altered when applied to PCDBF induced cultures. Production of amino nitrotoluene isomers was greatly enhanced in induced cultures as compared to uninduced controls, as was the conversion of radiolabeled 2,4-DNT to relatively more polar metabolites. To some extent, the results with H4IIE cells parallel those reported for animals exposed to 2,4-DNT after induction of cytochrome P-450 AHH activity. The preliminary findings suggest that with further development and validation, H4IIE cultures could be of use in characterizing metabolites that result from exposure to chemical mixtures involving a P-450 (1A1) inducer.
Mitchell
W R
WR
Health Effects Research Branch, U.S. Army Environmental Hygiene Agency, Fort Detrick, Frederick, MD 21702, USA.
Burrows
E P
EP
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001572:Benzofurans / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004136:Dinitrobenzenes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D008113:Liver Neoplasms / Q000473:pathology; D008163:Luminescent Measurements; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D004136:Dinitrobenzenes; C016403:2,4-dinitrotoluene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C038890:2,3,4,7,8-pentachlorodibenzofuran