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Different impact of p53 and p21 on the radiation response of mouse tissues

Oncogene volume 19, pages 3791–3798 (2000)Cite this article

Abstract

Mammalian tissues differ dramatically in their sensitivity to genotoxic stress, although the mechanisms determining these differences remain largely unknown. To analyse the role of p53 and p21 in determination of tissue specificity to DNA damage in vivo, we compared the effects of γ radiation on DNA synthesis on whole-body sections of wild type, p53-deficient and p21-deficient mice. A dramatic reduction in 14C-thymidine incorporation after γ irradiation was observed in the majority of rapidly proliferating tissues of wild type and p21−/− but not in p53−/− mice, confirming the key role of p53 in determination of tissue response to genotoxic stress in vivo and suggesting that p53-mediated inhibition of DNA synthesis does not depend on p21. Rapid radiation induced p53-dependent apoptosis was mapped to the areas of high levels of p53 mRNA in radiation sensitive tissues analysed (white pulp in the spleen and bases of crypts in small intestine), indicating that p53 regulation at the mRNA level is a determinant of cellular sensitivity to genotoxic stress. High p53 mRNA expression is inherited as a recessive trait in cell–cell hybrids suggesting the involvement of a negative control mechanism in the regulation of p53 gene expression.

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Acknowledgements

We thank Roman Kondratov for helpful comments and Jason Hill for help in manuscript preparation. This work was supported by grants from the National Institutes of Health CA75179 and Quark Biotech, Inc. to AV Gudkov.

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Authors and Affiliations

  1. Department of Molecular Genetics, University of Illinois at Chicago, Chicago, 60607, Illinois, IL, USA

    Elena A Komarova & Andrei V Gudkov

  2. Surgical Oncology, University of Illinois at Chicago, Chicago, 60607, Illinois, IL, USA

    Konstantin Christov

  3. Quark Biotech, Inc., Nes Ziona, Israel

    Alexander I Faerman

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  1. Elena A Komarova
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  2. Konstantin Christov
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  3. Alexander I Faerman
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  4. Andrei V Gudkov
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Komarova, E., Christov, K., Faerman, A. et al. Different impact of p53 and p21 on the radiation response of mouse tissues. Oncogene 19, 3791–3798 (2000). https://doi.org/10.1038/sj.onc.1203717

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