Induction of DNA double-strand breaks by 8-methoxycaffeine: cell cycle dependence and comparison with topoisomerase II inhibitors.
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 microM 8-MOC was approximately 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.
Russo
P
P
Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Cimoli
G
G
Valenti
M
M
De Sessa
F
F
Parodi
S
S
Pommier
Y
Y
D002110:Caffeine / Q000031:analogs & derivatives* / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D013601:T-Lymphocytes / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D059005:Topoisomerase II Inhibitors; D002110:Caffeine; C066637:8-methoxycaffeine; D004247:DNA