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 evaluat ed in the rectal mucosa from patients with extensive and long-standing ulcerative colitis. METHODS. Twenty-six patients with extensive disea se for more than 7 years and 11 healthy controls were included. Global DNA methylation was assessed as the capacity of the DNA test to incor porate [H-3]methyl groups from [H-3]-S-adenosyl-methionine in the pres ence of Sss1 methylase. A higher incorporation reflects a lower stale of intrinsic methylation, DNA ploidy, S-phase fraction, and proliferat ive index (PI = S + G(2)M) of the cell cycle were analyzed by flow cyt ometry. RESULTS. Incorporation of the [H-3]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 now cytometry, all samples showed a diploid p attern, bur S-phase fraction and the proliferative index values were s ignificantly 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 exacerbati ons of the disease (P < 0.005), and there was a trend among those pati ents who had disease for longer than 20 years to present with increase d cellular proliferation compared with those with a shorter evolution of disease (P > 0.05). CONCLUSIONS. DNA hypomethylation and proliferat ive activity are increased in this group of patients, supporting the c oncept that their colonic mucosa undergoes epigenetic and kinetic chan ges that might predispose these individuals to develop colorectal neop lasms. However, it cannot be ruled out that these markers solely refle ct hyperproliferation associated with active inflammation. (C) 1996 Am erican Cancer Society.