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 Scopus citations

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

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Theophylline reversal of alkylator-induced replicon initiation inhibition: no correlation with DDP-induced cytotoxicity'. Together they form a unique fingerprint.

  • Cite this