Formation of 2-chloroinosine from guanosine by treatment of HNO(2) in the presence of NaCl.
We investigated the reaction of Guo with nitrous acid in the presence of NaCl. When 1 mM Guo was incubated with 100 mM NaNO(2) and 2M NaCl in sodium acetate buffer at pH 3.2 and 37 degrees C, 2-chloroinosine (2-Cl-Ino) was produced 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 conditions, GMP and dGuo gave rise to the corresponding 2-chloro derivatives with comparable yields. All the 2-chloro derivatives were fairly stable (t(12)>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-HNO(2) system, was employed as a starting compound. When 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.
Suzuki
T
T
Institute of Advanced Energy, Kyoto University, Gokasho, 611-0011, Uji, Japan.
Ide
H
H
Yamada
M
M
Morii
T
T
Makino
K
K
D004063:Digestion; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D007288:Inosine / Q000138:chemical synthesis*; D007700:Kinetics; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism; D009608:Nitrous Acid / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D013274:Stomach Neoplasms / Q000209:etiology
D009573:Nitrites; D006151:Guanosine; D012965:Sodium Chloride; D007288:Inosine; D009608:Nitrous Acid