# ZINC DEFICIENCY AND RELATED FACTORS IN ESOPHAGEAL CANCER

> **NIH NIH R01** · MALLORY INSTITUTE OF PATHOLOGY · 1992 · $254,985

## Abstract

The dramatic worldwide variation in esophagal cancer incidence implicates a
variety of factors in the etiology of this disease and provides the
opportunity to test these factors experimentally.  The intractability of
the disease to conventional treatment methods underlines the importance of
attempting to understand whether and how these factors may alter the course
of this neoplasm.  The availability of a well-established animal model for
esophagel carcinogenesis makes this effort possible.

This research project is designed to further examine the ability of zinc
deficiency, a factor associated to this neoplasm, to enhance
methylbenzylnitrosamine (MBN)-induced esophageal carcinogenesis.  Zinc
deficiency signficantly enhances this carcinogenic process when applied
only through the end of dosing or after dosing is complete, indicating an
effect during different stages of the process.  Zinc deficient hyperplasia
can enhance the process at three stages:  (1) immediately prior to
carcinogen exposure by making cells more vulnerable to MBN; (2) during or
after dosing by preventing proper repair of damaged DNA; and (3) by
promoting tumor growth.  Previous experiments showed different patterns of
DNA synthesis in three dietary groups which produced different tumor
incidences.  Each pattern was consistent with tumor results to a certain
extent; further experimentation is required to clarify the results.  Zinc
deficiency may also exert its effect by altering adduct levels and
persistence, particularly of the promutagenic base 06-methylguanine.  A
number of enzymes, including polymerases, are zinc dependent and are
affected during a zinc deficiency; this may be another way in which zinc
deficiency may exert an effect.  An understanding of repair activity in
terms of the post dosing DNA synthesis patterns of inhibition and
enhancement, will clarify the importance of both of these factors.  Zinc
deficiency may also affect the enzymes that metabolize MBN and the
microflora and inflammatory response seen in the esophagus.  By further
limiting the time of zinc deficiency and measuring the above factors in
these diet-switched groups these experiments will clarify whether zinc
deficiency exerts its enhancing effect at a critical time point or
cumulatively and what the role of these factors is in this process.

## Key facts

- **NIH application ID:** 3179564
- **Project number:** 5R01CA040080-06
- **Recipient organization:** MALLORY INSTITUTE OF PATHOLOGY
- **Principal Investigator:** PAUL M. NEWBERNE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $254,985
- **Award type:** 5
- **Project period:** 1985-09-30 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179564

## Citation

> US National Institutes of Health, RePORTER application 3179564, ZINC DEFICIENCY AND RELATED FACTORS IN ESOPHAGEAL CANCER (5R01CA040080-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179564. Licensed CC0.

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