Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous mice

Jared M. Fischer, Susan B. Robbins, Sasi S. Kannamkumarath, Mustafa Al-Zoughool, Saundra L. Stringer, Glenn Talaska, Joseph A. Caruso, Peter J. Stambrook, James R. Stringer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Exposure to inorganic arsenic in drinking water is linked to cancer in humans, but the mechanism of arsenic-induced cancer is not clear. Arsenic is not a powerful point mutagen, but can cause chromosome malsegregation and mitotic recombination, two events that can cause loss of tumor suppressor alleles and thereby contribute to the evolution of cancerous cells. To determine whether arsenic increases the frequency of allele loss due to either malsegregation or mitotic recombination in vivo, Aprt+/- hybrid mice were exposed to sodium arsenite (10 mg/L) in their drinking water for 10 weeks. To determine whether arsenic enhances the action of a known mutagen, half of the arsenic-treated mice were exposed to benzo[a]pyrene (BaP) for 8 weeks by skin painting (500 nmoles/ week). Cells were taken from painted dorsal skin and cultured in the presence of 2,6-diaminopurine (DAP), to select colonies lacking adenosine phosphoribosyl transferase (Aprt) activity. The frequency of DAP-resistant (DAPr) colonies varied substantially within the treatment groups, but there was no significant difference between the groups. Analysis of DNA from DAPr colonies suggested that mitotic recombination contributed to the loss of wild-type Aprt allele. Whether arsenic or BaP enhanced or diminished the frequency of this process could not be deduced from these data.

Original languageEnglish (US)
Pages (from-to)334-344
Number of pages11
JournalEnvironmental and Molecular Mutagenesis
Volume47
Issue number5
DOIs
StatePublished - Jun 1 2006

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Keywords

  • Adenosine phosphoribosyl transferase
  • Arsenic
  • Genetic instability
  • Loss of heterozygosity
  • Mutation

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

Cite this

Fischer, J. M., Robbins, S. B., Kannamkumarath, S. S., Al-Zoughool, M., Stringer, S. L., Talaska, G., Caruso, J. A., Stambrook, P. J., & Stringer, J. R. (2006). Exposure of mice to arsenic and/or benzo[a]pyrene does not increase the frequency of Aprt-deficient cells recovered from explanted skin of Aprt heterozygous mice. Environmental and Molecular Mutagenesis, 47(5), 334-344. https://doi.org/10.1002/em.20212