# DNA REPAIR AND RESISTANCE TO PLATINUM DRUG TOXICITY

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1987 · $66,225

## Abstract

This research represents an investigation of the mechanisms of action of
the cancer chemotherapeutic platinum coordination complexes, as well as
investigation of the mechanisms of cellular resistance.  Three cell lines
will be used:  a) a murine leukemia L1210 cell line that is sensitive to
the action of both cis-diaminedichloroplatinum(II) (cis-DDP) and
diaminocyclohexaneplatinum analogues (DACH-Pt), b) an L1210 cell line
specifically resistant to cis-DDP (L1210/DDP), c) an L1210 cell line
specifically resistant to DACH-Pt (L1210/DACH).  The intention is to
compare these three cell lines with respect to the uptake and DNA binding
of the drugs and the subsequent ability of DNA repair processes to effect
removal of the lesions.  The interaction of cis-DDP with DNA has now been
fully characterized.  These studies were made possible by synthesis of a
radiolabeled analogue of cis-DDP, namely
[3H]-cis-dichloro(ethylenediamine)platinum(II) (cis-DEP) a drug to which
L1210/DDP is similarly resistant.  DNA repair inhibitors will be used to
elucidate the involvement of specific DNA repair pathways in L1210 cells
that have been incubated with [3H]-cis-DEP.  An attempt will be made to
purify the repair enzymes and assess any difference between the sensitive
and resistant cells.  Studies on DACH-Pt will be initiated by
characterizing its interaction with nucleosides and purified DNA using
enzyme digestions and high pressure liquid chromatography separation of the
adducts.  To facilitate these studies it is proposed to synthesize
[3H]-DACH-Pt.  This drug can then be used to investigate DNA repair
processes that might be different in L1210/DACH cells.  A further aspect
will be to analyze specific proteins that are crosslinked to DNA by the
platinum analogues and to compare their rates of repair.

## Key facts

- **NIH application ID:** 3173544
- **Project number:** 5R01CA036039-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **SAM.gov UEI:** G15AG3BLLMH4
- **Principal Investigator:** ALAN R EASTMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $66,225
- **Award type:** 5
- **Project period:** 1983-06-01 → 1988-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173544

## Citation

> US National Institutes of Health, RePORTER application 3173544, DNA REPAIR AND RESISTANCE TO PLATINUM DRUG TOXICITY (5R01CA036039-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173544. Licensed CC0.

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