DNA hypomethylation and proliferative activity are increased in the rectal mucosa of patients with long-standing ulcerative colitis.

BACKGROUND

DNA methylation and DNA cytometric parameters were evaluated in the rectal mucosa from patients with extensive and long-standing ulcerative colitis.

METHODS

Twenty-six patients with extensive disease for more than 7 years and 11 healthy controls were included. Global DNA methylation was assessed as the capacity of the DNA test to incorporate [3H]methyl groups from [3H]-S-adenosyl-methionine in the presence of Sss1 methylase. A higher incorporation reflects a lower state of intrinsic methylation. DNA ploidy, S-phase fraction, and proliferative index (PI = S + G2M) of the cell cycle were analyzed by flow cytometry.

RESULTS

Incorporation of the [3H]methyl groups into DNA was 10-fold higher in patients compared with controls (P < 0.001) and was significantly higher in patients with histologically active disease (P = 0.02). With regard to flow cytometry, all samples showed a diploid pattern, but S-phase fraction and the proliferative index values were significantly increased in patients compared with controls (P = 0.0007 and P = 0.003, respectively). A positive correlation was found between S-phase fraction and proliferative index and the number of exacerbations of the disease (P < 0.005), and there was a trend among those patients who had disease for longer than 20 years to present with increased cellular proliferation compared with those with a shorter evolution of disease (P > 0.05).

CONCLUSIONS

DNA hypomethylation and proliferative activity are increased in this group of patients, supporting the concept that their colonic mucosa undergoes epigenetic and kinetic changes that might predispose these individuals to develop colorectal neoplasms. However, it cannot be ruled out that these markers solely reflect hyperproliferation associated with active inflammation.