Posttreatment with sodium arsenite alters the mutational spectrum induced by ultraviolet light irradiation in chinese hamster ovary cells

Jia‐Ling ‐L Yang*, Mei‐Fang ‐F Chen, Cheng-Wen Wu, Te‐Chang ‐C Lee

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Arsenic, a potent carcinogen, fails to induce gene mutations in mammalian cells. However, posttreatment of ultraviolet light (UV) irradiated cells with sodium arsenite synergistically enhances the mutation frequency on the hypoxanthine (guanine) phosphoribosyltransferase locus. To investigate the molecular mechanism of the comutagenic effects of sodium arsenite, we characterized the alterations of nucleotide sequences in 30 UV‐induced and 39 sodium arsenite enhanced hprt mutants from Chinese hamster ovary K1 cells by direct sequencing of mRNA‐PCR amplified cDNA. The majority of sequence alterations derived from UV irradiation (80%) and from sodium arsenite posttreatment (70%) were single base substitutions. UV irradiation induced all types of base substitutions. Among them, 57% were transversions. The frequency of transversions increased to 70% in sodium arsenite enhanced mutants. While base substitutions observed in UV‐induced mutants were evenly distributed along with the whole coding region, exons 3 and 8 were most frequently mutated in sodium arsenite enhanced mutants. Sodium arsenite posttreatment did not alter the strand bias for mutation induction, i.e., 73% and 78%, of the mutations were located on the non‐transcribed strand in UV‐induced and sodium arsenite enhanced mutants, respectively. In contrast to UV‐induced mutations, bases at the 5' position of TT and the 3' position of CT sequences were the most frequent mutation sites observed in sodium arsenite enhanced mutants. We hypothesize that sodium arsenite may interfere with the process of mutation fixation of TT and CT dimers during DNA replication. © 1992 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)156-164
Number of pages9
JournalEnvironmental and Molecular Mutagenesis
Volume20
Issue number3
DOIs
StatePublished - 1 Jan 1992

Keywords

  • UV light
  • arsenite
  • comutagenicity
  • mutations
  • polymerase chain reaction

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