engleski

Histological distribution of acrolein-2-deoxyadenosine in human colon adenomas, carcinomas and non-malignant colon epithelium

Lipid peroxidation (LPO) has important role in colon carcinogenesis, while acrolein was found to be associated with transition of benign into malignant colon tumors. Our recent findings also show the increase of acrolein-protein adducts in the non-malignant colon epithelium in the vicinity of colon carcinomas. To see if this process of aldehyde based LPO damage affects also nucleic acids we used recently developed monoclonal antibody (mAb21) against the acrolein-modified DNA, which recognizes mostly acrolein modified 2'-deoxyadenosin (dA). Following tumors were analyzed: 1) tubular adenomas (N=10), 2) villotubular low grade adenomas (N=23), 3) villotubular high grade adenomas (N=18), 4) Duke's A carcinomas (N=19), Duke's B carcinomas (N=10) and Duke's C carcinomas (N=12) as well as 9 samples of normal colon and 33 colon tissue samples around carcinomas. In normal colon epithelium nuclear acrolein-dA positivity could hardly be found at all, while weak cytoplasmic immunopositivity was noticed often. In tumorous epithelium cytoplasmic acrolein-dA immunopositivity increased gradually with grade of dysplasia from benign tubular adenomas to carcinomas. Cytoplasmatic immunopositivity was high in carcinomas irrespective of the tumor grade (Dukes A, B or C). On the contrary, the level of nuclear acrolein-dA was higher in less dysplastic adenomas (tubular adenomas and low-grade villotubular adenomas), than in high-grade villotubular adenomas and colon carcinomas. Consequently, for advanced carcinomas (Dukes B and C) identical raise of both cytoplasmatic and nuclear acrolein-dA adducts was observed. As in case of previously described acrolein-protein aducts, acrolein-dA adducts confirmed the spread of LPO from carcinoma into adjacent non-malignant colon epithelium.

lipid peroxidation; acrolein-2-deoxyadenosine; colona adenoma; s colon carcinomas

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