Cytogenetic study of the induction mechanism of chromosome-type aberrations by 1-beta-D-arabinofuranosylcytosine.
Treatment of human lymphocytes in the G(1) phase with 1-beta-D-arabinofuranosylcytosine (AraC) results in the formation of chromosome-type aberrations, e.g., dicentric or ring chromosomes. Generally, it is accepted that DNA double-strand breaks (DSBs) cause chromosome-type aberrations. However, AraC lacks the functional groups necessary to induce such breaks, suggesting that it does not induce DSBs directly. In this study, we show that induction of DSBs is not mediated by direct action by AraC on DNA. Second, we demonstrate that the induction of DSBs or chromosome-type aberrations by AraC in human lymphocytes is inhibited by cycloheximide (CHM), an inhibitor of protein synthesis. These data suggest that newly synthesized proteins in AraC-treated lymphocytes mediate the induction of the DSBs. Thus, we suggest that AraC-induced endonucleolytic protein(s) in lymphocytes mediate the formation of chromosome-type aberrations.
Sekizawa
Koichi
K
Laboratory of Cytogenetics, Faculty of Health Sciences, Kyorin University, 476 Miyashita-cho, Hachioji, Tokyo 192-8508, Japan. sekizawa@kyorin-u.ac.jp <sekizawa@kyorin-u.ac.jp>
Suzuki
Toshimitsu
T
Kishi
Kunikazu
K
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003513:Cycloheximide / Q000494:pharmacology; D003561:Cytarabine / Q000633:toxicity*; D003582:Cytogenetics; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D009153:Mutagens; D011500:Protein Synthesis Inhibitors; D003561:Cytarabine; D003513:Cycloheximide