Theophylline release of replicon initiation inhibition by nitrosoureas correlates with the synergistic killing in L1210 leukemia in vitro

Jonathan M Ducore, Barry S. Rosenstein

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

This report demonstrates the synergistic killing of murine L1210 leukemia in vitro by BCNU and theophylline as has previously been reported in vivo. Synergism is also seen with the related nitrosourea CNU plus theophylline. As measured on alkaline sucrose gradients and by pH-step alkaline elution, the nitrosourea-induced inhibition of DNA replicon initiation is completely reversed in the presence of theophylline. DNA interstrand crosslinking, the damage which usually correlates with nitrosourea cytotoxicity, is not increased by the combination of nitrosourea plus theophylline. At high nitrosourea doses, this interstrand crosslinking is reduced in the presence of theophylline. At least part of the mechanism of the two-drug synergism is the theophylline release of nitrosourea-induced DNA initiation inhibition. Some of the results have been presented at the Annual Meeting of the American Association for Cancer Research.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMutation Research DNA Repair Reports
Volume146
Issue number1
DOIs
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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