title: DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis.
abstract: OBJECTIVE
  The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions.
  
  
  METHODS
  Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level.
  
  
  RESULTS
  The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00).
  
  
  CONCLUSIONS
  Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.
authors.affiliation: Postgraduate Programme Strictu Senso in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: José Ricardo
authors.initials: JR
authors.lastname: Scalise
authors.affiliation: Postgraduate Programme Strictu Senso in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Regina Caeli Guerra
authors.initials: RC
authors.lastname: Poças
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Thamy Pelatieri
authors.initials: TP
authors.lastname: Caneloi
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: Lopes
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Danilo Toshio
authors.initials: DT
authors.lastname: Kanno
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Mayara Gonçalves
authors.initials: MG
authors.lastname: Marques
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Júlio Cesar Martins
authors.initials: JC
authors.lastname: Valdivia
authors.affiliation: Scientific Initiation Student, Scientific Initiation Programme, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Felipe Rodrigues
authors.initials: FR
authors.lastname: Maximo
authors.affiliation: Department of Pathology, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: José Aires
authors.initials: JA
authors.lastname: Pereira
authors.affiliation: Postgraduate Programme Strictu Senso in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil.
authors.forename: Marcelo Lima
authors.initials: ML
authors.lastname: Ribeiro
authors.affiliation: Postgraduate Programme Strictu Senso in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil. depriolli@terra.com.br.|, Rua São Vicente 614. Jardim Paulista, Atibaia, SP, Brazil, CEP: 12947-390. depriolli@terra.com.br.
authors.forename: Denise Gonçalves
authors.initials: DG
authors.lastname: Priolli
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Adenocarcinoma; Adenoma; DNA damage; Immunohistochemistry; Tumor suppressor protein p53