# METABOLIC ACTIVATION OF UNSUBSTITUTED HYDROXAMIC ACID

> **NIH NIH R01** · BARBARA ANN KARMANOS CANCER INSTITUTE · 1990 · $143,560

## Abstract

Certain hydroxamic acids with the structure of ArCONHOH or RCONHOH
are mutagenic for bacteria and mammalian cells, and teratogenic in
experimental animals, and must, therefore, be regarded as potential
environmental hazards.  Yet, little is known in regard to the
biotransformation of these compounds to reactive species.  Our
previous results showed that 2-NHA is a strong direct mutagen for
S. typhimurium TA98 and that O-acetylation increased its
mutagenicity.  Results from the experiments conducted in the
initial granting period have demonstrated that 2NHA-OAc underwent
Lossen rearrangement at 37 degree, pH 7; the mutagenicity of 2-NHA
is not dependent on its acetylatyion to an O-acetate; that these
compounds can be activated independently to form DNA adducts in
bacteria; H202 mediated peroxidation can activate these mutagens
in a cell-free system and form adducts with nucleic acids.
Therefore, it is hypothesized that 1) hydroxamic acids and their
O-acetates are potential environmental genotoxins for humans
because of their activation by oxidative enzymes, and 2) the
activation mechanisms of hydroxamic acids may involve peroxidation
and that of the O-acetates may involve the lossen rearrangement and
peroxidation.  Our experimental approaches are:  A. Carry our the
Ames test using S. typhimurium TA98 in the presence of mammalian
peroxidative enzymes to determine the effects of peroxidation on
the mutagenicies of these compounds.  B. Reaction of these
compounds with the DNA of tissue slices of ram seminal vesicle,
which is rich in prostaglandin H synthase activity, and rat liver,
which has little of this peroxidase activity, to assess the
importance of the peroxidative reactions.  C.  To investigate the
peroxidative metabolic activation by bacterial enzymes by use of
the Ames test and added H202, as well an nucleic acid binding
assays using bacterial enzyme preparations.  D. DNA adducts
produced from 2-NHA and its O-acetate in Salmonella, in ram seminal
vesicle and rat liver, and form reactions with DNA with or without
enzyme-mediation, will be identified.  Results obtained from these
studies will aid in the elucidation of activation mechanisms of
this class of compounds.

## Key facts

- **NIH application ID:** 3175808
- **Project number:** 5R01CA037885-06
- **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:** 1990
- **Award amount:** $143,560
- **Award type:** 5
- **Project period:** 1985-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175808

## Citation

> US National Institutes of Health, RePORTER application 3175808, METABOLIC ACTIVATION OF UNSUBSTITUTED HYDROXAMIC ACID (5R01CA037885-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3175808. Licensed CC0.

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