# NITROSAMINE METABOLISM IN THE ESOPHAGUS

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1988 · $144,635

## Abstract

We will study the metabolism and action of methyl-n-amylnitrosamine (MNAN)
in the esophagus as follows:  (1) We will examine the production of hydroxy
and keto metabolites of MNAN in freshly removed esophagus, forestomach and
other tissues of rodents.  We will complete studies of changes with age of
this metabolism in key tissues of suckling rats and hamsters, determine
whether these changes are due to intrinsic or extrinsic factors, examine
effects of agents that induce individual P-450s, and determine
configurations of the hydroxy-MNAN metabolites.  (2) We will develop
systems for culturing adult rat esophagus, while still maintaining MNAN
metabolism.  We will study MNAN metabolism in cultures of newborn and adult
rat forestomach, hamster forestomach and hamster esophagus, and by freshly
incubated adult and fetal human esophagus, and study effects of inducers
and other agents on these cultures.  (3) We will examine MNAN metabolism by
rat liver and esophageal microsomes and reconstituted cytochrome P-450
("P-450") systems to determine which P-450s metabolize MNAN.  Gel
electrophoresis and specific antibodies will identify the individual P-450s
in adult and developed esophagus and forestomach.  (4) We will examine MNAN
alkylation of DNA to give 06- and N7 alkylguanine and 04-alkylthymine,
using 3H-MNAN or radioimmunoassay.  In vivo persistence of alkylated bases
in esophageal DNA will be measured, and DNA alkylation by 2- and
4-oxo-MNAN.  (5) We will determine whether MNAN is taken up more
extensively than dimethylnitrosamine by rat esophagus.  (6) We will compare
carcinogenicity of MNAN injected into newborn, 3-day-old and adult rats and
hamsters, test for carcinogenicity of 2- and 4-oxo-MNAN in adult rats, and
determine whether inducers can affect MNAN carcinogenicity.

These studies are designed to investigate (a) why MNAN is a specific
carcinogen for the rat esophagus, (b) what intrinsic or extrinsic factors
control the striking changes in MNAN metabolism from newborn to adult rats
and hamsters, and (c) whether human esophagus could be susceptible to
nitrosamine carcinogenesis.

## Key facts

- **NIH application ID:** 3173216
- **Project number:** 5R01CA035628-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **SAM.gov UEI:** G15AG3BLLMH4
- **Principal Investigator:** SIDNEY S MIRVISH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $144,635
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173216

## Citation

> US National Institutes of Health, RePORTER application 3173216, NITROSAMINE METABOLISM IN THE ESOPHAGUS (5R01CA035628-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173216. Licensed CC0.

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