[Caffeine inactivation of mammalian cells in the S phase of the mitotic cycle due to anomalous replicon initiation during the inhibition of the elongation of replicating DNA].
Chinese hamster cells were treated with an inhibitor of DNA synthesis (hydroxyurea or arabinoside-cytesine) in non-toxic concentrations for 20 hours in the presence or absence of caffeine (2 mM). Under these conditions caffeine considerably inactivates the cells. If cells are synchronized by hydroxyurea (0.25 mM) in the S-phase of mitotic cycle, the addition of caffeine kills all the S-phase cells, while gamma-irradiation or novobiocine treatment markedly decreases the sensibilizing effect of caffeine. These findings permit us to conclude that cell inactivation is due to anomalous reinitiation of DNA synthesis stimulated by caffeine in the presence of drugs which inhibit the DNA chain elongation.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors*; D004261:DNA Replication / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays; D006918:Hydroxyurea / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects* / Q000528:radiation effects; D008938:Mitosis / Q000187:drug effects* / Q000528:radiation effects; D009675:Novobiocin / Q000494:pharmacology; D012093:Replicon / Q000187:drug effects* / Q000528:radiation effects
D003561:Cytarabine; D009675:Novobiocin; D002110:Caffeine; D004247:DNA; D006918:Hydroxyurea
Inaktivatsiia kofeinom kletok mlekopitaiushchikh v S-faze mitoticheskogo tsikla, obuslovlennaia anomal'noĭ initsiatsieĭ replikonov pri tormozhenii élongatsii replitsiruiushcheĭsia DNK.