# ACETYLATION PHARMACOGENETICS--ARYLAMINES AND DNA DAMAGE

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1992 · $190,852

## Abstract

The major objective of this proposal is to test the hypotheses that genetic
differences in the activation of arylamine carcinogens are important
determinants of DNA damage and the formation of DNA-carcinogen adducts, and
that DNA-adduct formation seen after short-term exposures to arylamine
carcinogens is a valid indicator of susceptibility to carcinogenesis in a
genetically defined animal model.  To test the first hypothesis intact
inbred and congenic mice of defined metabolic genotype will be exposed to
2-aminofluorene under a number of exposure conditions and the formation of
2-AF-DNA adducts in the target tissues (liver and bladder) will be
measured.  The second hypothesis will be tested by a separate in vivo study
of the development of tumors in target tissues in acetylator congenic mice
exposed to 2-AF.

Additional objectives include determining if a polymorphism in N-oxidation
of arylamines exists in mice and it is an important determinant of tissue
and DNA damage from these compounds.  The role of other enzymes of
arylamine metabolism in modulating the risk of damage by this ubiquitous
class of chemicals will also be examined.

An important goal of this proposal is to establish inbred acetylator
congenic mice as models for human colo-rectal cancer related to
heterocyclic arylamine food mutagens.

The inbred acetylator congenic mouse strains provide a unique resource for
the investigations proposed because they enable a study of this hereditary
trait isolated from other polymorphic traits affecting the disposition of
and response to arylamines.  The analysis of the consequences of arylamine
exposure using this animal model should enable a more accurate assessment
of the effects attributable to acetylator genes in relation to other genes
than heretofore possible, and may also facilitate the acquisition of
information about differences in susceptibility to human cancers of
environmental origin that is stymied because of the ethical constraints and
methodological difficulties that prevail.

## Key facts

- **NIH application ID:** 3177646
- **Project number:** 5R01CA039018-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** WENDELL W WEBER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $190,852
- **Award type:** 5
- **Project period:** 1985-01-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177646

## Citation

> US National Institutes of Health, RePORTER application 3177646, ACETYLATION PHARMACOGENETICS--ARYLAMINES AND DNA DAMAGE (5R01CA039018-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177646. Licensed CC0.

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