Spontaneous mutation frequency and pattern in Big Blue® mice fed a vitamin E-supplemented diet

Stephen R. Moore, Kathleen A. Hill, Petra W. Heinmoller, Asanga Halangoda, Makoto Kunishige, Victoria L. Buettner, Kenneth S. Graham, Steve S. Sommer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue® mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,1-α- tocopherol acetate from conception until 3 months of age. Using the standard Big Blue® protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacl transgene. The α-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C → T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d- α-tocopherol acetate.

Original languageEnglish (US)
Pages (from-to)195-200
Number of pages6
JournalEnvironmental and Molecular Mutagenesis
Volume34
Issue number2-3
DOIs
StatePublished - Nov 8 1999

Keywords

  • Antioxidants
  • Diet
  • Oxidative DNA damage
  • Spontaneous mutation
  • Vitamin E
  • lacl transgene

ASJC Scopus subject areas

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

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