5-Azacytidine-induced 6-thioguanine resistance at the gpt locus in AS52 cells: cellular response.
Treatment of AS52 cells with 5-azacytidine resulted in an induction of 6-thioguanine-resistant [6TG] colonies, which reached a maximum by an expression time of 9 days. Dose responses for both cytotoxicity and mutation induction were determined following treatment with 5-azacytidine. At 20 microM treatment, 5-azacytidine exposure resulted in about 50% survival. Mutant frequency reached a maximum of 10 microM. At concentrations between 10 and 20 microM, 5-azacytidine was a potent mutagen but did not exhibit a dose response. Although many compounds both induce cell death and affect the growth rate of cells, 5-azacytidine specifically induced cell death and did not affect the doubling time of the surviving treated cell population.
Spencer
D L
DL
Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Caspary
W J
WJ
Hines
K C
KC
Tindall
K R
KR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D001374:Azacitidine / Q000633:toxicity*; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics*; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics*; D029968:Escherichia coli Proteins; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D010430:Pentosyltransferases; D011506:Proteins; D013866:Thioguanine / Q000494:pharmacology*; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D009153:Mutagens; D011506:Proteins; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; D013866:Thioguanine; D001374:Azacitidine