# PROMOTION OF LUNG TUMORS BY BHT

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 1987 · $203,457

## Abstract

Only a few agents have been unambiguously demonstrated to be promoters in
experimetal animals; butylated hydroxytoluene (BHT) is one of these.  BHT
promotes hepatomas in rats and pulmonary adenomas in mice.  Small amounts
of BHT are needed for pomotion and substances from diverse chemical classes
can serve as initiators.  BHT is added to foods because of its useful
antioxidant properties; the dietary consumption of BHT is at one of the
highest levels for any synthetic additive.  It is thus of practical
importance to understand the mechanisms by which BHT promotes tumors, and
of considerable scientific interest to expand the study of tumor promotion
to include lung.  Two sensitive analytical techniques, HPLC and GC/MS, will
be applied to analyze the BHT metabolites produced in vivo and in vitro.
The toxic and tumor promoting effects of BHT vary between inbred strains,
species and organs.  By comparing the metabolites produced in a variety of
systems with the physiological effects of BHT in that system, we hope to
clearly identify and distinguish between the toxic and tumor promoting
derivatives of this compound.  Protein phosphorylation regulates many
biological activities and protein kinases have been directly implicated in
cell transformation by tumor viruses.  Tumor promotors may also disrupt
normal cellular control of protein phosphorylation.  The
calmodulin-dependent and phospholipid-dependent Ca++-activated kinases will
be characterized in the lungs of mice after urethane (initiator) and BHT
(promoter) administration.  Aphotoaffinity analog of cyclic GMP,
8-N3-(32P)cGMP, will be used to monitor the kinases activated by cyclic
GMP.  A photoaffinity analog of ATP, 8-N3-(32P)ATP will be used to monitor
other kinases in whole lung extracts and in isolated populations of the
Type 2 cells from which the adenomas are derived.  Glucocorticoids inhibit
proliferation of Type 2 cells, accelerate differentiation of these cells,
and inhibit the toxic effects of BHT on mouse lung.  Whether
glucocorticoids affect the promoting activity of BHT will be tested.  Using
a new procedure for in vitro autoradiography, the effects of BHT on the
cellular location of pulmonary glucocorticoid receptors will be determined.

## Key facts

- **NIH application ID:** 3171334
- **Project number:** 2R01CA033497-05A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **SAM.gov UEI:** SPVKK1RC2MZ3
- **Principal Investigator:** ALVIN M MALKINSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $203,457
- **Award type:** 2
- **Project period:** 1982-09-01 → 1991-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171334

## Citation

> US National Institutes of Health, RePORTER application 3171334, PROMOTION OF LUNG TUMORS BY BHT (2R01CA033497-05A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3171334. Licensed CC0.

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