# METABOLISM AND GENETOXICITY OF NITROSAMINES

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1990 · $131,542

## Abstract

The cyclic N-nitrosamine N-nitrosopyrrolidine (NPy) is a potent
animal carcinogen that is found in mainstream and sidestream
tobacco smoke.  NPy is highly mutagenic in vitro in the Ames assay
in the presence of an appropriate metabolizing enzyme system.
Unlike acyclic N-nitrosamines, NPy does not yield a high level of
DNA adducts' and to date no DNA adduct has been identified.  Based
on our observation that NPy induces single-strand breaks and/or
alkali labile lesions, we have formulated the working hypothesis
that NPy genotoxicity is derived from the formation of transient
DNA adducts.  We propose to test this hypothesis by: 1) determining
if NPy is metabolized in vitro to N-nitroso-2-pyrrolidone (2-oxo-
NPy) via an intermedite 2-hydroxy-NPy; 2) characterizing the in
vivo genotoxicity of NPy with specific emphasis on the formation
of DNA-protein and DNA-DNA crosslinks; 3) determining which
metabolite of NPy is responsible for the crosslinking; 4)
determining if NPy affords phosphotriesters and/or
apurinic/apyrimidinic sites with any base or sequence specificity
using DNA of known sequence; and 5) determining the chemical
stability and reactivity of synthetic site specific
phosphotriester-modified oligodeoxynucleotides that are suspected
to be produced from NPy.  The results of these studies will provide
basic knowledge concerning the carcinogenicity of an N-nitroso
compound that apparently does not yield stable DNA adducts.

## Key facts

- **NIH application ID:** 3177523
- **Project number:** 5R01CA038976-06
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **SAM.gov UEI:** G15AG3BLLMH4
- **Principal Investigator:** BARRY GOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $131,542
- **Award type:** 5
- **Project period:** 1985-01-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177523

## Citation

> US National Institutes of Health, RePORTER application 3177523, METABOLISM AND GENETOXICITY OF NITROSAMINES (5R01CA038976-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177523. Licensed CC0.

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