DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis

Abstract

Purpose

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).

Conclusion

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.

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