Metabolism of the chlorofluorocarbon substitute 1,1-Dichloro-2,2,2-trifluoroethane by rat and human liver microsomes: The role of cytochrome P450 2E1
- Universitaet Wuerzburg, Wuerzburg (France)
1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons. The atmospheric lifetime of HCFC-123 is expected to be much shorter than those of chlorofluorocarbons; however, due to its lower stability and the presence of carbon-hydrogen bonds, metabolism of HCFC-123 and its analogue halothane in rat and human liver microsomes. [sup 19]F-NMR studies showed that trifluoroacetic acid is a major metabolite of HCFC-123. Besides trifluoroacetic acid, chlorodifluoroacetic acid and inorganic fluoride were identified as products of the enzymatic oxidation of HCFC-123 in rat and human liver microsomes by [sup 19]F-NMR and mass spectrometry. These metabolites were not detected in incubations with halothane. HCFC-123 and halothane were transformed by liver microsomes from untreated rats at low rates. Microsomes from ethanol-and pyridine-treated rats metabolized both HCFC-123 and halothane at much higher rates. These microsomes also exhibited high rates of p-nitrophenol oxidation. p-Nitrophenol is a model substrate mainly oxidized by P450 rates of p-nitrophenol oxidation. p-Nitrophenol is a model of substrate mainly oxidized by P450 2E1 to p-nitrocatechol. Samples of human liver microsomes showed considerable differences in the extent of HCFC-123,p-nitrophenol oxidation, and chlorzoxazone hydroxylation. In human liver microsomes, rabbit anti-rat P450 2E1 IgG recognized a single protein band corresponding in apparent molecular weight to human P450 2E1. Immunoblot analysis revealed considerable heterogeneity in the P450 2E1 protein content of the human liver samples. Trifluoroacetic acid formation from HCFC-123 and halothane and p-nitrocatechol formation from p-nitrophenol were significantly reduced by the P450 2E1 inhibitor diethyldithiocarbamate. p-Nitrophenol also inhibited halothane and HCFC-123 oxidation in both rat and human liver microsomes. 41 refs., 8 figs., 3 tabs.
- OSTI ID:
- 6955836
- Journal Information:
- Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 7:2; ISSN CRTOEC; ISSN 0893-228X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Pentahaloethane-based chlorofluorocarbon substitutes and halothane: Correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation
Exposure to the chlorofluorocarbon substitute 2,2-dichloro-1,1,1- trifluoroethane and the anesthetic agent halothane is associated with transient protein adduct formation in the heart
Related Subjects
550500 -- Metabolism
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
CELL CONSTITUENTS
CHLOROFLUOROCARBONS
CYTOCHROMES
FLUORINATED ALIPHATIC HYDROCARBONS
HALOGENATED ALIPHATIC HYDROCARBONS
KINETICS
LIVER CELLS
MAMMALS
MATERIAL SUBSTITUTION
METABOLISM
MICROSOMES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OZONE
PIGMENTS
PROTEINS
RATS
REACTION KINETICS
RESPONSE MODIFYING FACTORS
RIBOSOMES
RODENTS
SOMATIC CELLS
VERTEBRATES