Formation of 2-chloroinosine from guanosine by treatment of HNO2 in the presence of NaCl

We investigated the reaction of Guo with nitrous acid in the presence of Na Cl. When 1 mM Guo was incubated with 100 mM NaNO2 and 2 M NaCl in sodium ac etate buffer at pH 3.2 and 37 degreesC, 2-chloroinosine (2-Cl-Ino) was prod uced in addition to oxanosine (Oxo) and xanthosine (Xao). The yield of 2-Cl -Ino was 0.033 mM at an incubation time of 2 h. Under the same reaction con ditions, GMP and dGuo gave rise to the corresponding 2-chloro derivatives w ith comparable yields. All the 2-chloro derivatives were fairly stable (t(1 /2) > 360 h) at physiological pH and temperature. To elucidate the reaction mechanism of the chlorination, the diazoate derivative of Guo, a reaction intermediate of the Guo-HNO2 system, was employed as a starting compound. W hen the diazoate was incubated with 2M NaCl in a neutral solution, 2-Cl-Ino was produced in addition to Oxo and Xao. These results suggest that the 2- chloro derivatives can be produced from foodstuffs in the human stomach and may have potential importance as a carcinogen causing gastric cancer. (C) 2001 Elsevier Science Ltd. All rights reserved.