# ROLE OF ETHANOL IN THE ETIOLOGY OF HEAD & NECK CANCER

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1991 · $115,414

## Abstract

Chronic alcohol and tobacco use have been positively associated with
increased risk for head and neck cancers in man.  The precise mechanism(s)
which account for this increased risk are not known.  Our working
hypothesis is that chronic alcohol consumption alters one or more
components of the microsomal mixed function oxygenase system resulting in
enhanced rates of metabolic e=activation of tobacco-associated
carcinogens.  Our studies have shown that ethanol consumption by hamsters
results in enhanced liver and target tissue (trachea) metabolism, enhanced
post-mitochondrial supernatant-mediated mutagenicity and carcinogenicity
(tracheal and nasal cavity) of N-nitrosopyrrolidine (NPYR).  The proposed
series of studies are designed to directly test the hypothesis that
enhanced metabolic activation of NPYR in target tissues results in
enhanced carcinogenicity in Syrian golden hamsters and to critically
examine the respective roles of alpha- and Beta-hydroxylation, and
denitrosation in the target site specificity of NPYR by examining both
target and non-target tissues for the alpha-hydroxylation of NPYR as well
as the induction of the isozyme of cytochrome P450 induced by ethanol that
is believed to participate in the metabolic activation of the N-
nitrosamines.  The link between ethanol consumption, metabolism, metabolic
activity and enhanced tumor incidence will be clearly delineated.  In
addition, since the microsomal metabolism of nicotine results in the
formation of reactive intermediates (iminium ion species) which have also
been suggested as intermediates for the clinical nitrosation of nicotine,
we plan to determine if in situ nitrosation of nicotine can be catalyzed
by isolated microsomes.  This pathway for nitrosamine formation would
result in the intracellular generation of N'-nitrosonornicotine (NNN), 4-
(methynitrosamino)-4-(3-pyridyl)butanone (NNK), and 4'-
(methylnitrosamino)-4-(3-pyridyl)butanol (NNA) from nicotine.  These
tobacco-specific nitrosamines can be found in both unburned tobacco as
well as mainstream and sidestream tobacco smoke and are known to cause
head and neck tumors as well as lung tumors in experimental animals.

## Key facts

- **NIH application ID:** 3170130
- **Project number:** 5R01CA032126-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** G DAVID MCCOY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $115,414
- **Award type:** 5
- **Project period:** 1982-04-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170130

## Citation

> US National Institutes of Health, RePORTER application 3170130, ROLE OF ETHANOL IN THE ETIOLOGY OF HEAD & NECK CANCER (5R01CA032126-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170130. Licensed CC0.

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