Anti-cytochrome P450 IIE1 (anti IIE1) and dimethyl sulfoxide inhibit acetaminophen and dimethylnitrosamine oxidation similarly

Conference · Mon Mar 11 04:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5307473

Jaw, S; Jeffery, E H ^[1]; Roberts, D W ^[2]

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1. Univ. of Illinois, Urbana (United States)
2. National Center for Toxicological research, Jefferson, AR (United States)

To evaluate specificity of dimethyl sulfoxide (DMSO), the authors compared anti IIE1 and DMSO inhibition of P450 oxidations. Hepatic microsomes from control and acetone-induced female Swiss-Webster mice were preincubated with polyclonal anti IIE1 or IgG for 20 min at 4C before addition of an NADPH-generating system, DMSO or buffer, and substrate (Ethylmorphine, EM; dimethylnitrosamine, DMN; or acetaminophen, AP; 1 mM final concentration). After 20 min at 37C, the incubations were terminated by adding 20% trichloroacetic acid or methanol. Formaldehyde was determined by the Nash method when using EM or DMN as substrate. AP-glutathione conjugate was determined by HPLC when using AP as substrate. Anti IIE1 and DMSO did not inhibit EM demethylation in control or acetone microsomes. However, DMSO inhibited DMN demethylation by 26% and 64% in control and 30% and 75% in acetone microsomes. Anti IIE1 inhibited DMN demethylation by 44% and 24% in control and acetone microsomes, respectively. DMSO inhibited AP metabolism by 31% and 56% and anti IIE1 inhibited AP metabolism by 33%, in control microsomes. The inhibitions of DMN and AP metabolism by anti IIE1 and DMSO were only additive at submaximal inhibitor concentrations and confirm that DMSO specifically inhibits IIE1 activity.

• OSTI ID: 5307473
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:4
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CHROMATOGRAPHY
DMSO
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
INHIBITION
LIQUID COLUMN CHROMATOGRAPHY
METABOLISM
MICROSOMES
MIXED-FUNCTION OXIDASES
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
RIBOSOMES
SEPARATION PROCESSES
SPECIFICITY
SULFOXIDES