title: Inhibitory effect of caffeine on potentially lethal damage repair in cisplatin-treated human osteosarcoma cells.
abstract: Human osteosarcoma cells, that were cultured to confluence and maintained under low nutrient conditions, showed potentially lethal damage repair after cisplatin treatment. This repair was inhibited by a non-toxic dose of caffeine. Flow cytometric analysis indicated that cisplatin-treated cells accumulated in the S phase by 24 hr, followed by accumulation in the G2/M phase. Caffeine inhibited the initial accumulation in the S phase and the release of cells from the G2/M block. DNA synthesis was also inhibited by the cisplatin treatment. The addition of caffeine significantly reversed this inhibition. The content of DNA-bound platinum decreased over time after cisplatin treatment. Caffeine did not influence platinum content, nor did it directly affect the DNA excision repair. Cisplatin inhibits DNA synthesis in the S phase, but caffeine reduces this inhibition. Caffeine-treated cells that pass through S phase are incapable of recovery.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yasutake
authors.forename: H
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: K
authors.initials: K
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: O
authors.initials: O
authors.lastname: Nikaido
authors.forename: T
authors.initials: T
authors.lastname: Mori
mesh_terms: D001859:Bone Neoplasms; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016195:G2 Phase; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D012516:Osteosarcoma; D016196:S Phase; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D002110:Caffeine; D002945:Cisplatin; D013936:Thymidine