1. ¹Department of Biochemistry & Molecular Pathology, Osaka City University Medical School, Osaka 545-8585, Japan
2. ²Department of Gastroenterology, Osaka City University Medical School, Osaka 545-8585, Japan
3. ³Department of Gastroenterology, Hyogo Medical School, Hyogo 663-8131, Japan
4. ⁴Department of Pathology, Hyogo Medical School, Hyogo 663-8131, Japan

Correspondence: Dr M Nishikawa, E-mail: nishikawa@med.osaka-cu.ac.jp

Received 24 February 2005; Revised 30 April 2005; Accepted 18 May 2005; Published online 14 June 2005.

Abstract

We recently reported that oxidative stress elicited by chronic inflammation increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with precancerous status. Since severe oxidative stress is elicited in the colorectal mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was investigated. Colorectal mucosal specimens were obtained from individuals with UC with and without colitic cancer and from control subjects. The frequency of mtDNA mutations was higher in colorectal mucosal specimens from patients with UC than that from control subjects. The levels of 8-hydroxy-2'-deoxyguanosine, a DNA adduct by reactive oxygen species, were significantly higher in UC than in control. Specimens from patients with colitic cancer contained a significantly higher number of mtDNA mutations. The present observations suggest that the injury followed by the regeneration of colorectal mucosal cells associated with chronic inflammation causes accumulation of mtDNA mutations. The increased instability of genes, including those on the mtDNA, is consistent with the high and multicentric incidence of colorectal cancer in individuals with UC. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation, and may be useful for the prediction of risk of carcinogenesis.