engleski

Pathomorphological distribution of acrolein in human colon tumors

Recent investigations found that acrolein, a lipid peroxidation product, could be rapidly incorporated into proteins, generating a carbonyl derivative as a marker of oxidative stress to proteins. Acrolein, an aldehyde that can be ubiquitously generated in biological systems, is extremely reactive and accumulates in a form covalently bound to proteins in vivo. Due to its biological effects it is considered to be a potent factor of carcinogenesis in particular if based on exogenous or iatrogenic pathology (cigarette smoking, dietary factors, etc.). As it is well known the colon carcinogenesis is influenced strongly by oxidative stress and lipid peroxidation, which was especially well documented for 4-hydroxynonenal, we studied possible differences in distribution of acrolein-protein adducts in human colon tissue and different types of tumors. Monoclonal antibody (acrolein-KLH antibody mAb5F6) was used at 2  g/ml on tissue sections of formalin-fixed paraffin embedded specimens that were deparaffinized, hydrated, and stained using a modified avidin– biotin peroxidase immunohistochemistry. Following tumors were analyzed: 1) tubular adenomas (N=24), 2) vilotubular low grade adenomas (N=24), 3) vilotubular high grade adenomas (N=20), 4) Duke’ s A carcinomas (N=19), Duke’ s B carcinomas (N=11) and Duke’ s C carcinomas (N=15) as well as 13 samples of normal colon tissues samples. The results obtained have shown that normal colon tissue, both epithelium and stroma are occasionally positive for acrolein. However, acrolein positivity was significantly less frequent in tubular and vilotubular low grade adenomas increasing gradually to normal distribution in high grade vilotubular adenomas and Duke’ s A stage carcinomas. Advanced stages of carcinomas (Duke’ s B and C) were again associated with less obvious acrolein presence in the tissues. Interestingly in Duke’ s A carcinomas the incidence of acrolein in malignant cells’ nuclei was more pronounced than in advanced stages of carcinomas (B & C). According to these findings we assume that, similar to 4-hydroxynonenal, acrolein may also play an important role in colon carcinogenesis both in early stage tumor development and its further progression. To understand further role of the aldehydes, both acrolein and 4-hydroxynonenal in colon carcinogenesis additional studies also on their physiological roles in cell growth control are needed.

acrolein; human colon tumors

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