UDP-glucuronosyltrasferases (UGTs) are detoxifying enzymes, which convert endogenous substrates, dietary constituents and potential carcinogens to inactive hydrophilic glucuronides. Although the liver is considered the most important organ for glucuronidation, UGTs are also expressed in extrahepatic tissues. Since UGTs may be important to protect cells from cancer in organs naturally exposed to potential carcinogens such as smoking and diet derivatives, we investigated the UGT expression in normal and malignant tissues from urinary bladder and large intestine. The study was carried out by immunohistochemistry, using an antiserum recognizing all the UGT1A isoforms. Our results showed that UGTs were highly expressed on the surfaces of the normal bladder as well as in normal large bowel mucosa. The neoplastic counterpart showed a general protein down-regulation associated with a different cellular localization. We found that 3/11 papillary and 3/6 invasive urothelial carcinomas were virtually negative, whereas 2/2 papillomas and 8/11 papillary bladder carcinomas still expressed the protein. In colon cancer the enzyme down-regulation was even more dramatic. In fact, a faint diffused cytoplasmic expression or scattered cell positivity was observed only in adenomas with low grade dysplasia (5/5) and in 2/11 carcinomas. Interestingly, 5/5 adenomas with high grade dysplasia, 9 carcinomas, the lymph nodes and liver metastases were UGT-negative, suggesting that the loss of UGT is associated with the early phase of neoplastic transformation. Based on our results we suggest that UGTs constitutive expression in the normal mucosa could protect these organs from carcinogens released in the bladder or introduced directly with the diet in the colon.

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