Suicide inactivation of rat liver aryl sulfotransferase IV (AST IV) by the sulfuric acid ester of N-hydroxy-2-acetylaminofluorene (NOH-AAF)

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

OSTI ID:5863362

Ringer, D P; Norton, T R; Self, R R ^[1]

---

1. Noble Foundation, Ardmore, OK (United States)

Rat liver NOH-AAf sulfotransferase activity is mediated by AST IV and causes the bioactivation of NOH-AAF to a highly reactive, mutagenic sulfuric acid ester form which putatively has a role in inducing liver cancer. Unexpectedly, AAF has been found to decrease liver NOH-AAF sulfotransferase activity in dietary protocols used to induce hepatocarcinogenesis. The authors have thus examined reaction-product, suicide inactivation of AST IV as a possible mechanism for the loss in sulfotransferase activity. In initial experiments, purified AST IV was found to undergo a PAPS-dependent binding with ({sup 14}C)-NOH-AAF. Alkaline hydrolysis and C18-HPLC analysis of the AST IV:AAF conjugates revealed that linkage primarily involved cysteine and methionine residues of AST IV. Experiments testing the effect of pretreatment of AST IV with NOH-AAF upon subsequent assay of sulfotransferase activity, showed that there was a NOH-AAF and PAPS dependent loss in AST IV sulfotransferase activity. These results demonstrate the highly reactive, sulfuric acid ester of NOH-AAF can covalently link with AST IV causing suicide inactivation of the enzyme, and suggests that it deserves consideration as an in vivo mechanism for loss of NOH-AAF sulfotransferase activity.

• OSTI ID: 5863362
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
FLUORENE
METABOLISM
TRANSFERASES
ENZYME ACTIVITY
CARBON 14 COMPOUNDS
CARCINOGENESIS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
RATS
SULFURIC ACID ESTERS
TRACER TECHNIQUES
ANIMALS
AROMATICS
BODY
CARBON COMPOUNDS
CHROMATOGRAPHY
CONDENSED AROMATICS
DIGESTIVE SYSTEM
ENZYMES
ESTERS
GLANDS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROTEINS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology