# PHARMACOGENETICS OF DRUG & CARCINOGEN METABOLISM

> **NIH NIH R01** · MOREHOUSE SCHOOL OF MEDICINE · 1988 · $152,469

## Abstract

Arylamine chemicals are a significant cause of occupation and
environment-related cancer in humans.  Arylamines are used as intermediates
in the synthesis of numerous organic compounds, as antioxidants in a host
of consumer products, and are released as pyrolysis products in the
combustion of protein and organic matter.  Critical risk determinants in
the development of chemical carcinogenesis from arylamines include
predisposing host factors in addition to exposure.  Recent human
epidemiological studies strongly suggest a genetic predisposition to
arylamine-induced bladder cancer, and to the more invasive forms of bladder
cancer, among slow acetylators.  Slow acetylation capacity is controlled by
two codominant alleles at a single locus.  Over one-half of all Black and
Caucasian Americans are slow acetylators.

Various acetyl transfer steps have been identified in the metabolic
activation and deactivation of arylamines to their ultimate carcinogenic
forms, including acetyl coenzyme.  A (AcCoA)-dependent intermolecular
N-acetylation of arylamines, O-acetylation of N-hydroxy-arylamines,
AcCoA-independent intramolecular N,O-acetyltransfer of arylhydroxamic
acids, and deacetylation of arylamides and arylhydroxamic acids.
Preliminary data suggest that the enzymatic capacity for N-and
O-acetylation capacity are controlled at a single and common genetic locus
and that they are catalyzed by common acetyltransferase isozymes.  To test
this hypothesis, we propose to construct Bio.  82.73/H/Natr and Bio.
1.5/Natr congenic inbred hamster strains.  Through comparisons between
these homozygous rapid acetylator congenic strains and their corresponding
homozygous slow acetylator background strains, we will make a direct
assessment of the role of the polymorphic N-acetylator gene locus on
various hepatic and extrahepatic acetyltransferase isozymes that catalyze
the acetylation and/or deacetylation of carcinogenic arylamines, and their
corresponding arylamides, arylhydroxylamines and arylhydroxamic acids.
Companion characterizations also will be carried out with acetylation
isozymes derived from human organ donors.

## Key facts

- **NIH application ID:** 3172387
- **Project number:** 5R01CA034627-05
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **SAM.gov UEI:** X5S7PNXMJMC7
- **Principal Investigator:** David W Hein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $152,469
- **Award type:** 5
- **Project period:** 1983-09-30 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172387

## Citation

> US National Institutes of Health, RePORTER application 3172387, PHARMACOGENETICS OF DRUG & CARCINOGEN METABOLISM (5R01CA034627-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172387. Licensed CC0.

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