The role of various nucleosides in the activation of 5-fluorouracil in gastric adenocarcinoma

Abstract

<p>The main metabolic pathways of anticancer drug 5-fluorouracil (5-FU) include its transformation to active<br />metabolites via attaching the naturally occurring pentose phosphates. It is known that different tissues use different<br />nucleosides as donators of pentose phosphates for activation of 5-FU. The objective of the present study was<br />determination of pentose phosphate sources for 5-FU metabolic transformation in gastric adenocarcinoma and<br />normal adjacent mucosa. 5-FU was incubated in vitro with one of the nucleosides (adenosine, uridine, thymidine)<br />and tumor or adjacent tissue homogenates obtained from patients with gastric adenocarcinoma. The concentration<br />of initial metabolites and the products of the pentose exchange reaction in the samples was determined before and<br />after the incubation by means of HPLC . Both in systems with tumor and normal tissue homogenates the reaction<br />of 2’-deoxyribose exchange between thymidine and 5-FU occurred resulting in equimolar production of 5-fluoro-2’-<br />deoxyuridine and thymine. In the model system containing adenosine free ribose-1-phosphate was formed; however,<br />the formation of nucleoside from 5-FU did not arise. It was also shown that mutual incubation of 5-FU and uridine<br />with gastric tissues homogenates did not result in the formation of 5-FUd. Among the examined natural nucleosides<br />it is only thymidine that serves as pentose phosphate source for the first step of the activation of 5-FU in gastric<br />adenocarcinoma and normal adjacent tissue.</p>