# HORMONES, RADIATION, AND MALIGNANT TRANSFORMATION

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1987 · $125,696

## Abstract

The long-term objective of this research is to elucidate the mechanisms of
low-dose radiation-induced carcinogenesis through studying its effects on a
series of specific membrane-associated pathways known to be rapidly
activated in whole or in part by the tumor promoting agents
12-0-tetradecanoyl-phorbol-13-acetate (TPA) and epidermal growth factor
(EGF), as well as by a variety of growth-promoting hormones and other
cell-stimulatory agents.  We will examine the effects of radiation on
levels of key components of these pathways:
Phosphatidylinositol-4,5-biphosphate, inositol-1,4,5-triphosphate,
diacylglycerols, and free cytoplasmic Ca2+, as well as on the activity of
the phosphorylating enzyme protein kinase C.  These levels/activities will
be assayed:  1) at selected times post-irradiation, to determine whether
any radiation-induced effects are rapidly produced (as expected from direct
membrane perturbations) or are produced at later times (expected if such
effects arise from radiation-produced alterations in gene expression); 2)
during a radiation-initiated/promotor (TPA, EGF, or the hormone
cortisone)-enhanced transformation regiment, to determine whether
initiating doses of radiation alter inositol phospholipid-associated
pathways known to be activated by selected tumor promoters; and 3) at
various post-irradiation times in the presence of large,
transformation-suppressing dietary protease inhibitors (the Bowman-Birk
inhibitor and the chick-pea inhibitor), which are likely to be
membrane-active and whose action in inhibiting specific steps in the series
of inositol phospholipid-related membrane-associated pathways could support
a role for such step(s) in carcinogenesis.  Additionally, we will perform a
series of radiation-induced transformation assays in the presence of
modulators of levels/activities of specific components (cytoplasmic (Ca2+,
protein kinase C) of the pathways studied, to ascertain whether altering
the availabiligy of these components affects the ability of cells to
undergo radiation-induced or radiation-initiated/promotor-enhanced
transformation.  Experiments will be performed in an in vitro system
utilizing the mouse embryo-derived C3H10T-1/2 cell line used extensively
for in vitro transformation research.  These studies will provide
information about whether there are direct or indirect effects of low-dose
radiation on membrane-associated cellular activation processes known to be
induced by tumor promotors, as well as elucidate the role of these
activation processes in low-dose radiation induced cell transformation as
it is promoted by hormonal and other promoting agents and inhibited by
dietary protease inhibitors.

## Key facts

- **NIH application ID:** 3172444
- **Project number:** 5R01CA034680-05
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** ANN R KENNEDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $125,696
- **Award type:** 5
- **Project period:** 1983-05-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172444

## Citation

> US National Institutes of Health, RePORTER application 3172444, HORMONES, RADIATION, AND MALIGNANT TRANSFORMATION (5R01CA034680-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172444. Licensed CC0.

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