Levels of dna damage are unaltered in mice overexpressing human catalase in nuclei

Samuel E. Schriner, Charles E. Ogburn, Annette C. Smith, Terry G. Newcomb, Warren C. Ladiges, Martijn E.T. Dollé, Jan Vijg, Ken Ichiro Fukuchi, George M. Martin

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Two types of transgenic mice were generated to evaluate the role of hydrogen peroxide in the formation of nuclear DNA damage. One set of lines overexpresses wild-type human catalase cDNA, which is localized to peroxisomes. The other set overexpresses a human catalase construct that is targeted to the nucleus. Expression of the wild-type human catalase transgene was found in liver, kidney, skeletal muscle, heart, spleen, and brain with muscle and heart exhibiting the highest levels. Animals containing the nuclear-targeted construct had a similar pattern of expression with the highest levels in muscle and heart, but with lower levels in liver and spleen. In these animals, immunofluorescence detected catalase present in the nuclei of kidney, muscle, heart, and brain. Both types of transgenic animals had significant increases of catalase activities compared to littermate controls in most tissues examined. Despite enhanced activities of catalase, and its presence in the nucleus, there were no changes in levels of 8OHdG, a marker of oxidative damage to DNA. Nor were there differences in mutant frequencies at a Lac Z reporter transgene. This result suggests that in vivo levels of H2O2 may not generate 8OHdG or other types of DNA damage. Alternatively, antioxidant defenses may be optimized such that additional catalase is unable to further protect nuclear DNA against oxidative damage. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)664-673
Number of pages10
JournalFree Radical Biology and Medicine
Volume29
Issue number7
DOIs
StatePublished - Oct 16 2000
Externally publishedYes

Keywords

  • 8OHdG
  • Catalase
  • Free radicals
  • Mutation
  • Oxidative damage
  • Transgenics

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Schriner, S. E., Ogburn, C. E., Smith, A. C., Newcomb, T. G., Ladiges, W. C., Dollé, M. E. T., Vijg, J., Fukuchi, K. I., & Martin, G. M. (2000). Levels of dna damage are unaltered in mice overexpressing human catalase in nuclei. Free Radical Biology and Medicine, 29(7), 664-673. https://doi.org/10.1016/S0891-5849(00)00352-X