# CYCLOSPORINE A:  PROMOTER OF LYMPHOMA INDUCTION

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1989 · $103,727

## Abstract

The major objective of the proposed study is to clarify the
mechanism of lymphoma development in patients receiving
immunosuppressive treatment.  Cyclosporine (CsA) is presently
one of the most successful immunosuppressants used in clinical
organ transplantation but its use has been shown to be associated
with the development of lymphomas.  During the past 2 years of
support, we demonstrated the promoting action of CsA for the
induction of murine lymphoid tumors of either T or B cell lineage
depending upon the types of initiating agents given.  We postulate
that the most plausible explanation for the promoting action of
CsA is its interference with T-cell maturation in the thymus and
its stimulation of B-cell proliferation in the lymph nodes.  In this
renewal application we will extend our studies in several
directions.  We will explore the mechanism underlying complex
interactions of chemical carcinogens, radiation and retroviruses in
the development of lymphoid tumors by exploiting the rat model
of Moloney murine leukemia virus-induced lymphomas in
conjunction with CsA as a tumor promoter.  We will determine
whether CsA has any effects on the induction of epithelial tumors
using the model of urethane induced pulmonary adenoma in mice.
We will further define the effects of CsA on T-cell maturation in
the thymus with the use of a flow cytometry and T-cell
differentiation antigens.  Attempts will be made to determine
whether selected thymic hormones may counteract the effects of
CsA on the thymus.  Functions of some of the cellular
protooncogenes have been implicated to the control of cellular
differentiation and/or cell proliferation.  We will investigate the
transcriptional expression of selected cellular protooncogenes in
thymocytes (thymus) and lymphocytes (lymph nodes) os CsA-
treated mice with or without initiation, to clarify to what extent
changes in protooncogene expression correlate with the
disturbance of thymocyte differentiation and proliferation of
lymphocytes.  These studies will provide better insight into not
only the mechanism of CsA-promotion of lymphoid malignancies
but also the basic aspects of CsA-action on immune systems.

## Key facts

- **NIH application ID:** 3173680
- **Project number:** 5R01CA036175-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** HISASHI SHINOZUKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $103,727
- **Award type:** 5
- **Project period:** 1984-07-01 → 1990-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173680

## Citation

> US National Institutes of Health, RePORTER application 3173680, CYCLOSPORINE A:  PROMOTER OF LYMPHOMA INDUCTION (5R01CA036175-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173680. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*