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© 1994 Oxford University Press

research-article

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

Patrizia Russo, Guido Cimoli, Monica Valenti 1, Fabio De Sessa 2, Silvio Parodi and Yves Pommier 1

Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro Genova 1-16132, Italy
1Department of Molecular Pharmacology DNA-Topology Section, NCI-NIH, Bethesda, MD 20892,USA
2Department of Bone Surgery Unita' Sanitana Locale Genova 3, I–16036, Genova , Italy

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 topoiso merase 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 {bsim}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.


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