Theophylline reversal of alkylator-induced replicon initiation inhibition

no correlation with DDP-induced cytotoxicity

Jonathan M Ducore, Barry S. Rosenstein

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The synergistic cytotoxic activity exhibited by bifunctional alkylating agents in the presence of methylxanthines has been associated with methylxanthine-induced reversal of alkylator-induced DNA replicon initiation inhibition. This has also beenseen with methylxanthines and ionizing irradiation. Methylxanthines do not appear exacerbate drug or ionizing radiation-induced damage. We report here a situation in which methylxanthine-induced reversal of DNA replicon initiation inhibition is not associated with increased cytotoxicity of the alkylator. Murine L1210 leukemia cells were assayed for cytotoxicity following treatment with either l-PAM or cis-DDP in the presence or absence of theophylline. Theophylline increased the cytotoxicity seen after l-PAM treatment but failed to increase the cis-DDP induced cytotoxicity. Analysis of pulse-labeled DNA on alkaline sucrose gradients revealed the expected decrease in DNA replicton initiation in L1210 cells treated with either l-PAM or cis-DDP. Theophylline had no effect on replicon initiation in untreated cells. Theophylline reversed the replicon initiation inhibition in cells treated with either l-PAM or cis-DDP. The reason for the apparent lack of added toxicity of the replicon initiation inhibition reversal in L1210 cells treated with theophylline and DDP is unknown.

Original languageEnglish (US)
Pages (from-to)117-121
Number of pages5
JournalMutation Research Letters
Volume141
Issue number2
DOIs
StatePublished - 1984
Externally publishedYes

Fingerprint

Replicon
Alkylating Agents
Cytotoxicity
Theophylline
Pulse amplitude modulation
DNA
Leukemia L1210
Ionizing radiation
Ionizing Radiation
Toxicity
Sucrose
methylxanthine
Irradiation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Medicine(all)

Cite this

Theophylline reversal of alkylator-induced replicon initiation inhibition : no correlation with DDP-induced cytotoxicity. / Ducore, Jonathan M; Rosenstein, Barry S.

In: Mutation Research Letters, Vol. 141, No. 2, 1984, p. 117-121.

Research output: Contribution to journalArticle

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