# ARYL SULFOTRANSFERASE IN DRUG AND XENOBIOTIC METABOLISM

> **NIH NIH R01** · UNIVERSITY OF IOWA · 1987 · $101,376

## Abstract

Sulfation of arylhydroxamic acids, arylhydroxylamines, and
benzylic alcohols is an essential step leading to their
biotransformation into chemically reactive, electrophilic
compounds which are capable of binding covalently to nucleophilic
sites on cellular macromolecules.  This covalent binding is the
initial step leading to various cytotoxic, mutagenic, and/or
carcinogenic responses.  One of the major goals of the research
described in this application is to provide an understanding of the
mechanisms involved in the regulation of the catalytic activities
and concentrations of the aryl sulfotransferse(s) that catalyze
sulfation of molecules containing arylhydroxamic acid,
arylhydroxylamine, and benzylic alcohol functional groups.  The
other goal of this research is to develop quantitative methods for
assessing the reactivity of the sulfate esters of these functional
groups.  Our long-term objective is to be able to accurately
predict sulfation, and subsequent reactivity of the sulfate ester,
for both new and existing drugs as well as other xenobiotics that
contain arylhydroxamic acid, arylhydroxylamine, and benzylic
alcohol functional groups.

The proposed research will utilize purified enzymes, isolated
hepatocytes, and immunochemical techniques to accomplish these
goals.  Regulation of aryl sulfotransferase (AST) IV activity will
be studied with the purified enzyme and with isolated rat
hepatocytes.  The relative participation of AST II and AST IV in
sulfation reactions catalyzed by isolated rat hepatocytes will also
be investigated.  Purified AST IV will be used to develop a
quantitative method for determining rate constants for reaction
of electrophilic sulfate esters with model nucleophiles.  Kinetic
constants will be determined for the AST IV-catalyzed sulfation
of N-hydroxy-2-acetylaminofluorene and N-hydroxy-2-
aminofluorene, as well as for the reaction of the resulting sulfate
esters with model nucleophiles.  Structure-activity studies will be
carried out for the AST IV-catalyzed sulfation of primary and
secondary arylhydroxylamines and aromatic dihydrodiols.
Immunochemical studies on AST will yield information on the
localizations and concentrations of AST II and AST IV in hepatic,
cutaneous, and respiratory tract tissues of untreated and
xenobiotic-treated rats.  Furthermore, the distribution of AST IV
in liver will be studied immunohistochemically after chronic
treatment of rats with 2-acetylaminofluorene.

## Key facts

- **NIH application ID:** 3176868
- **Project number:** 2R01CA038683-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **SAM.gov UEI:** Z1H9VJS8NG16
- **Principal Investigator:** MICHAEL W DUFFEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $101,376
- **Award type:** 2
- **Project period:** 1984-08-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176868

## Citation

> US National Institutes of Health, RePORTER application 3176868, ARYL SULFOTRANSFERASE IN DRUG AND XENOBIOTIC METABOLISM (2R01CA038683-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176868. Licensed CC0.

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