# PLATINUM ANTITUMOR AGENTS: SYNTHESIS AND CELL BIOLOGY

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1990 · $121,913

## Abstract

The goal is:  1) to develop new platinum drugs with increased tumor
selectivity and increased cytocidal efficiency in combination with
therapeutic radiation and 2) to study the biological interactions of
platinum complexes with cellular components, especially DNA.  A selected
series of tetrachloroplatinum (II) nuclear staining (+)- charged molecule
complexes will be prepared by the reaction of potassium
tetrachloroplatinate with two molar equivalents of the dyes.  Cytotoxicity,
radiation sensitization and post-irrradiation effects of the platinum
complexes will be studied under oxygenated and hypoxic conditions.  Special
attention will be given to potential lethal damage repair inhibition of
x-irradiation, bleomycin and adriamycin.  A murine and two human cell lines
will be used for these experiments.  In vivo studies will center on the
efficacy of these agents in combination with radiation therapy.  Drugs will
be administered either 1 hr prior to or immediately following radiation
treatment.  The experiments will first be carried out at the maximum
non-toxic dose of the drug and with single dose (10, 20 or 30 Gy) radiation
treatment.  The most promising agents will also be examined ina
fractionated x-ray protocol with drug administered before or after each
fraction.  Antitumor activity of the complexes will be assessed in three
murine tumors.  To study drug penetration and to determine if these agents
are producing true dose modification in combination with x-rays, tumor
excision-cell survival assays will be performed.  Density gradient
separation of tumor subpopulations will be used to assess the effect of the
treatment combinations on the hypoxic cell subpopulation of the tumor.
Bone marrow survival will be determined by CFU-GM.  Kidneys will be
examined histologically.  The binding of these complexes to DNA and the
effects of these complexes on DNA repair in the presence and absence of
x-rays will be assessed by two methods:  1) DNA alkaline elution of cells
treated in vitro, and 2) digestion with T4 DNA polymerase (3' - 5')
associated exonuclease of 5'-labelled, drug-treated DNA fragments of
defined sequence.

## Key facts

- **NIH application ID:** 3174131
- **Project number:** 5R01CA036508-07
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** BEVERLY A. TEICHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $121,913
- **Award type:** 5
- **Project period:** 1984-01-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174131

## Citation

> US National Institutes of Health, RePORTER application 3174131, PLATINUM ANTITUMOR AGENTS: SYNTHESIS AND CELL BIOLOGY (5R01CA036508-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174131. Licensed CC0.

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