Induction of 6-thioguanine resistance in human cells treated with N-acetoxy-2-acetylaminofluorene

Shiu L. Huang, Michael W. Lieberman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Induction of 6-thioguanine resistance was studied in human cells treated with the direct-acting chemical carcinogen N-acetoxy-2-acetylaminofluorene (NA-AAF). At low concentrations (2.5-7.5 μM) induction of resistant clones was linear and followed one-hit kinetics, while at 10 μM the yield of resistant clones was higher and appeared to result from the combination of one-hit and two-hit kinetics. A study of about 50 resistant clones revealed that most had reduced levels of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity (25-85% of controls) and were able to use exogenous hypoxanthine for growth ("Type II mutants," deMars, 1974); a few had very low HGPRT activity (1-8% of controls) and were unable to use exogenous hypoxanthine ("Type I mutants"). Use of [914-C]NA-AAF allowed us to examine the frequency of induction of thioguanine resistance as a function of binding to DNA (μmole AAF/mole DNA-P). Calculations from these data suggest that most "hits" on the HGPRT locus do not result in detectable mutations: At three different levels of binding and induced mutation frequency, the yield was 2.5-3 detectable mutants/10 000 molecules of acetylaminofluorene bound to the HGPRT locus. These data suggest that most bound acetylaminofluorene molecules either produce no change in the primary sequence of DNA (possibly as a result of repair or correct "read through" by the DNA polymerase) or result in changes which are phenotypically undetectable.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume57
Issue number3
DOIs
StatePublished - Jan 1 1978

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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