# OXYGEN RADICALS IN MINERAL DAMAGE/TUMOR PROMOTION

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 1987 · $125,436

## Abstract

Bronchogenic carcinoma is the leading cause of cancer deaths in man.  Both
epidemiologic and experimental studies suggest the importance of asbestos
and other minerals as cofactors in the development of this neoplasm and
mesothelioma, a tumor occurring rarely in the general population but
frequently in asbestos workers.  Over the previous period of funding, the
principal investigator has documented in tracheal bronchial epithelial
cells exposed to asbestos a constellation of promoter-like effects
resembling the actions of phorbol esters on target cells.  These include
initial cell damage, inflammatory changes and regenerative hyperplasia and
metaplasia.  In recent studies, the prevention of asbestos-associated
cytotoxicity has been accomplished using scavengers of superoxide (02) and
the hydroxyl (OH.) radical.  This project is designed to test the
hypothesis that active oxygen species play a role in asbestos-induced cell
damage and promotion in target cells, i.e. those giving rise to
bronchogenic carcinoma and mesothelioma.  Specifically, we will address the
questions:  1) Do specific scavengers of oxygen free radicals prevent
asbestos induced damage to mesothelial cells?  2) Do mesothelial and
epithelial cell types contain various scavenger enzymes (SOD, catalase,
glutathione peroxidase) and is the activity of endogenous SOD altered after
exposure of cells to asbestos?  3) Can administration of exogenous
scavengers of oxygen free radicals prevent fiber-associated hyperplasis,
squamous metaplasia and inflammation in tracheal (and mesothelial) organ
cultures and grafts?  4) Does asbestos cause release of OH., H202 and 02
from both epithelial and mesothelial cells?  and 5) is actual fiber-cell
contact necessary for generation of oxygen free radicals?  The importance
of mineral chemistry, size and shape in the causation of biological
responses will be addressed by using two types of asbestos (crocidolite and
chrysotile) in comparison with their nonfibrous analogs (riebeckite and
antigorite, respectively).  Sized preparations (i.e. long (greater than
10Mu) vs short (less than 2Mu) of chrysotile also will be assessed.  In
addition glass particles will be included in experiments as an example of
an amorphous, non-carcinogenic dust.

Elucidation of the properties of minerals which are important in tumor
promotion is intrinsic to understanding the process of multi-stage
carcinogenesis in lung.  The results of this proposal will provide a
mechanistic framework for preventive and therapeutic approaches using
scavengers of oxygen free radicals in man.

## Key facts

- **NIH application ID:** 3171348
- **Project number:** 5R01CA033501-06
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **SAM.gov UEI:** Z94KLERAG5V9
- **Principal Investigator:** Brooke Taylor Mossman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $125,436
- **Award type:** 5
- **Project period:** 1982-08-01 → 1988-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171348

## Citation

> US National Institutes of Health, RePORTER application 3171348, OXYGEN RADICALS IN MINERAL DAMAGE/TUMOR PROMOTION (5R01CA033501-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171348. Licensed CC0.

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