Induction of DNA double-strand breaks by 8-methoxycaffeine: Cell cycle dependence and comparison with topoisomerase II inhibitors

Patrizia Russo, Guido Cimoli, Monica Valenti, Fabio De Sessa, Silvio Parodi, Yves Pommier

Research output: Contribution to journalArticle

Abstract

We have studied the ability of 8-methoxycaffeine (8-MOC) - one of the most effective caffeine derivatives in inducing chromosomal aberrations - to induce DNA double strand breaks (DSB) in purified human T lymphocytes during the cell cycle. Etoposide- or ellipticine-mediated DNA break frequency was used as a parameter of topoisomerase II activity. DNA-DSB induced by either 8-MOC or VP16 or ellipticine rose co-ordinately with the level of DNA topoisomerase II and with the onset of DNA replication. At concentrations between 10 and 50 μM 8-MOC was ~75% as active in terms of DSB as VP16 and ellipticine. By contrast with VP16 and ellipticine, 8-MOC was not cytotoxic. In conclusion, our data suggest that 8-MOC is an agent that efficiently induces DNA-DSB at non-toxic concentrations, and without direct inhibition of topoisomerase II.

Original languageEnglish
Pages (from-to)2491-2496
Number of pages6
JournalCarcinogenesis
Volume15
Issue number11
Publication statusPublished - Nov 1994

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ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

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