L. Gloria et al., DNA HYPOMETHYLATION AND PROLIFERATIVE ACTIVITY ARE INCREASED IN THE RECTAL MUCOSA OF PATIENTS WITH LONG-STANDING ULCERATIVE-COLITIS, Cancer, 78(11), 1996, pp. 2300-2306
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.