title: The DNA methylation inhibitor 5-azacytidine modulates 6-thioguanine toxicity in mammalian cells.
abstract: In order to assess the effects of combining two antimetabolites used separately to treat human leukemias, we carried out an experimental study by exposing V79 Chinese hamster cells, a 6-thioguanine (6-tG)-sensitive cell line, to sequential and concurrent treatments with 5-azacytidine (5-azaC) and 6-tG. In this paper, we demonstrate that there is a clear dependency for the way in which this combination was tested. Pre-treatment with 5-azaC made V79 cells more resistant to 6-tG by a substantial reduction in 6-tG incorporation into DNA; this effect could still be detected for several cell divisions after the removal of 5-azaC, and was achieved neither by reduced cell growth nor by the induction of hypoxanthine-guanine-phosphoribosyltransferase (HGPRT-) mutants. The reverse order of treatment produced a higher toxic effect than exposure to each prodrug alone.
authors.affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo A. Monroy, Università di Palermo, Viale delle Scienze Parco d'Orleans, Palermo 90128, Italy. giscian@mbox.unipa.it
authors.forename: Giulia
authors.initials: G
authors.lastname: Sciandrello
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
authors.forename: Giusi
authors.initials: G
authors.lastname: Barbata
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001374:Azacitidine / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004357:Drug Synergism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013866:Thioguanine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D001374:Azacitidine