5-Azacytidine-induced 6-thioguanine resistance at the gpt locus in AS52 cells: cellular response

Environ Mol Mutagen. 1996;28(2):100-6. doi: 10.1002/(SICI)1098-2280(1996)28:2<100::AID-EM5>3.0.CO;2-J.

Abstract

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.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity
  • Azacitidine / toxicity*
  • Bacterial Proteins / drug effects*
  • Bacterial Proteins / genetics*
  • CHO Cells
  • Cell Division / drug effects
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Drug Resistance / genetics*
  • Escherichia coli Proteins
  • Mutagenesis / drug effects
  • Mutagens / toxicity
  • Mutation
  • Pentosyltransferases
  • Proteins*
  • Thioguanine / pharmacology*
  • Time Factors

Substances

  • Antimetabolites, Antineoplastic
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Mutagens
  • Proteins
  • Pentosyltransferases
  • Gpt protein, E coli
  • Thioguanine
  • Azacitidine