# METABOLIC ACTIVATION OF UNSUBSTITUTED HYDROXAMIC ACID

> **NIH NIH R01** · BARBARA ANN KARMANOS CANCER INSTITUTE · 1987 · $144,755

## Abstract

Unsubstituted hydroxamic acids (ArCONHOH orRCONHOH) are mutagenic for
bacteria and mammalian cells and, therefore, are potential carcinogens.  It
is generally believed that the binding of chemicals to DNA is an early step
in many of the processes of mutagenesis and carcinogenesis.  For one class
of known mutagens and carcinogens, i.e., arylhydroxamic acid, (ArNOHCOR),
which is structurally different from the N-unsubstituted hydroxamic acid,
(ArCONHOH), the activation pathways leading to DNA adduct formation and
carcinogenesis have been well studied.  In contrast, very little is known
about the reaction of unsubstituted hydroxamic acids with macromolecules
under biological and chemical conditions.

In this proposal, 2-naphthohydroxamic acid will be used as a model
compound, because it is one of the most mutagenic hydroxamic acids of this
class.  The appropriately labeled 2-napthohydroxamic acid and its
derivatives wil be used to explore the reaction pathways responsible for
their metabolic activation to yield adducts with DNA of bacteria and cell
free systems.  One potential of this compound to elicit a genotoxic
response in animals will also be tested by determining the extent and types
of adduct formation of this compound with the macromolecules of rat liver
and kidney in vivo.  The carcinogenicity of 2-naphthohydroxamic acid will
be tested with newborn CD rats by S.C. injections, thus establishing the
carcinogenic or non-carcinogenic nature of this model compound.

The results obtained from this project will provide the basis for future
studies of mechanisms of activation and carcinogenicity of these hydroxamic
acids.

## Key facts

- **NIH application ID:** 3175806
- **Project number:** 5R01CA037885-03
- **Recipient organization:** BARBARA ANN KARMANOS CANCER INSTITUTE
- **SAM.gov UEI:** NAJZPZ4GN5B3
- **Principal Investigator:** MEI-SIE LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $144,755
- **Award type:** 5
- **Project period:** 1985-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175806

## Citation

> US National Institutes of Health, RePORTER application 3175806, METABOLIC ACTIVATION OF UNSUBSTITUTED HYDROXAMIC ACID (5R01CA037885-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175806. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*