Oxidative stresson mucosal cells of the colon, resulting from the action of free radicals presentin the intestinal lumen, represents one of the initial phenomena in colorectalcarcinogenesis, because it may induce gene mutations relating to cell cyclecontrol. Quantification of the oxidative damage to the DNA in colorectal cancerpatients has been little studied so far.
OBJECTIVE: To measure the levels of oxidative damage to the DNA in cellsisolated from the colon mucosa in colorectal patients, and to compare normaland neoplastic tissues and make correlations with anatomopathological variables.
METHOD: Thirty colorectal adenocarcinoma patients (eighteen women) ofmean age 60.6 ± 15.5 years who consecutively underwent operations performedby the same surgical team between 2005 and 2006 were studied. The oxidativedamage to the DNA was evaluated by means of the alkaline version of the cometassay (single-cell gel electrophoresis), from fragments of normal and neoplasticcolon tissue that were obtained immediately after removal of the surgical specimen.The extent of breakages of the DNA helices was assessed using an image intensificationmethod, on 200 randomly chosen cells (100 from each tissue sample), by meansof the Komet 5.5 program. The Tail Moment (T.M) measured in each cell quantitativelyrepresented the extent of the oxidative damage to the DNA. The statistical analysison the variables considered was performed by means of the Student t, chi-squaredand Kruskal-Wallis tests, with a significance level of 5% (p<0.05).
RESULTS: It was found that, for all the patients studied, the cellsobtained from the neoplastic tissue presented oxidative damage to the DNA thatwas greater than in the cells from normal tissue. The cells isolated from theneoplastic mucosal tissue of the colon presented extension of DNA strand breakagesignificantly greater (T.M. = 2.532 ± 0.945) than did the cells isolatedfrom normal tissue (T.M. = 1.056 ± 0.460) (p=0.00001; C.I. 95%: -1.7705to 1.1808). It was found that the patients at earlier stages of the Dukesand TNM classifications presented higher levels of oxidative damage than didthose at more advanced stages (p=0.04 and p=0.001, respectively).
CONCLUSIONS: The cells obtained from normal tissue of colorectal cancerpatients presented signs of oxidative damage to the cell DNA, although at significantlower levels than in the neoplastic cells.