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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerates sarcoma development in Trp53+/- mice.

Chronic inflammation is a recognized risk factor for human cancer at various sites because of persistent oxidative and nitrative tissue damage. Trp53(+/-) mice show the predisposition to tumor development, such as sarcomas and lymphomas, compared with Trp53(+/+) mice. We investigated the effects of chronic inflammation, especially oxidative and nitrative stress, induced by subcutaneous implantation of a plastic plate (10 x 5 x 1 mm) as a foreign body on tumorigenesis in Trp53(+/-) and Trp53(+/+) mice. The plastic plates were implanted at the age of about 11 weeks. Thirty out of 38 Trp53(+/-) mice (79%) developed sarcomas around the implant (mean time of tumor appearance was 45.8 +/- 12.0 weeks of age), whereas only one of 10 Trp53(+/+) mice with an implant (10%) developed a tumor, at 56 weeks. No sarcomas developed at a sham-operation site. Two of 10 Trp53(+/-) mice with no implant (20%) also developed three sarcomas spontaneously at 77, 81 and 84 weeks. Increased immunostaining for markers of oxidative and nitrative stress (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-nitroguanine and 3-nitrotyrosine) and expression of inducible nitric oxide synthase in tumor cells and inflammatory cells were detected in implant-induced sarcomas compared with spontaneous sarcomas in Trp53(+/-) mice. Furthermore, p53 loss of heterozygosity was observed in 26 out of 29 implant-induced sarcomas (90%). These results indicate that implanted foreign bodies significantly enhanced sarcoma development in Trp53(+/-) mice, and this may be associated with increased oxidaive and nitrative stress. Loss of the remaining wild-type p53 allele and loss of p53 function appears to be, at least in part, underlying molecular mechanisms during the development of sarcomas at the implantation site in Trp53(+/-) mice. Such implant-induced sarcoma development in Trp53(+/-) mice could be useful for studying molecular mechanisms and developing new strategies for chemoprevention in human carcinogenesis induced by chronic inflammation and/or foreign bodies.[1]

References

  1. Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerates sarcoma development in Trp53+/- mice. Tazawa, H., Tatemichi, M., Sawa, T., Gilibert, I., Ma, N., Hiraku, Y., Donehower, L.A., Ohgaki, H., Kawanishi, S., Ohshima, H. Carcinogenesis (2007) [Pubmed]
 
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