8-methoxycaffeine-induced protein-associated DNA breaks in isolated L1210 cell nuclei.
8-methoxycaffeine (8-MOC) is a caffeine derivative more potent than its parental compound in inducing chromosomal aberrations. 8-MOC has been postulated to produce chromosomal aberrations by DNA topoisomerase II inhibition. The effect of 8-MOC on nuclear DNA were studied by alkaline elution experiments and compared with those of Ellipticine and Adriamycin (ADR). Like Ellipticine and ADR, 8-MOC induced single strand breaks (SSBs), double strand breaks (DSBs), and DNA-protein cross-links (DPCs) in a bell-shaped manner with respect to drug concentration. As in the case of ADR and Ellipticine, 8-MOC induced equal SSB and DPC frequencies. These results could suggest that 8-MOC induces DNA breaks by interacting with DNA topoisomerase II or with a similar DNA metabolism enzyme.
Zignaigo
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Istituto Nazionale per la Ricerca sul Cancro, Sezione di Genova.
Vigani
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Billi
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Brega
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I
Piccini
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Poggi
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L
Parodi
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Russo
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P
D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002869:Chromosome Aberrations; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D004611:Ellipticines / Q000494:pharmacology; D007364:Intercalating Agents / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure
D003432:Cross-Linking Reagents; D004611:Ellipticines; D007364:Intercalating Agents; D059005:Topoisomerase II Inhibitors; C034192:ellipticine; D002110:Caffeine; C066637:8-methoxycaffeine; D004317:Doxorubicin