UV light is a major cause of human skin cancers. Nitrite and nitrate are well-known potential risk factors for gastric cancer. Little attention has been paid to the relationship between UV light and nitrite or nitrate on cancer. We examined the effects of nitrite and nitrate on the damage to nucleosides and DNA induced by UV light from a mercury lamp and by sunlight at neutral pH. A biologically relevant dose of nitrite and nitrate increased the generation of nucleobases and malondialdehyde on the reaction of nucleosides and DNA with UV light. The efficiency of nitrite enhancing the reaction was higher than that of nitrate at low doses. The contribution of the hydroxyl radical as the reactive species was suggested from the results of the inhibitory effects of hydroxyl radical scavengers. Nitrite and nitrate also enhanced the formation of nucleobases and malondialdehyde from DNA induced by sunlight. In the presence of 5 muM nitrite, the concentration in human skin cells, the product yields by sunlight were 5-10-fold greater than those in the absence of nitrite. The addition of 80 muM NO(3)(-), a concentration in human skin cells, also increased the yields significantly. Nitrite and nitrate may play a role in enhancing the genotoxic effects of UV light in humans.

Hypobromous acid (HOBr) is formed by eosinophil peroxidase and myeloperoxidase in the presence of H2O2, Cl(-), and Br(-) in the host defense system of humans, protecting against invading bacteria. However, the formed HOBr may cause damage to DNA and its components in the host. When a guanine nucleoside (3',5'-di-O-acetyl-2'-deoxyguansoine) was treated with HOBr at pH 7.4, spiroiminodihydantoin, guanidinohydantoin/iminoallantoin, dehydro-iminoallantoin, diimino-imidazole, amino-imidazolone, and diamino-oxazolone nucleosides were generated in addition to an 8-bromoguanine nucleoside. The major products were spiroiminodihydantoin under neutral conditions and guanidinohydantoin/iminoallantoin under mildly acidic conditions. All the products were formed in the reaction with HOCl in the presence of Br(-). These products were also produced by eosinophil peroxidase or myeloperoxidase in the presence of H2O2, Cl(-), and Br(-). The results suggest that the products other than 8-bromoguanine may also have importance for mutagenesis by the reaction of HOBr with guanine residues in nucleotides and DNA.

When the ultrasound of 42 kHz was irradiated on a neutral mixture of 2'-deoxycytidine, 2'-deoxyguanosine, 2'-deoxythymidine, and 2'-deoxyadenosine, concentrations of all the nucleosides decreased. Addition of NaCl to the system had no effect. NaBr suppressed the reactions for all the nucleosides, but the efficiency of 2'-deoxyguanosine was low. NaI suppressed the reactions for all the nucleosides more effectively. A comparison with the results of the effects of halides on the reaction of nucleosides by a Fenton system suggested that only half of the nucleoside damage in the ultrasound-irradiated solution was caused by hydroxyl radicals formed from water by the sonication.

When 8-bromoguanosine was incubated with cysteine at pH 7.4 and 37 °C, a previously unidentified product was formed as a major product in addition to guanosine. The product was identified as a cysteine substitution derivative of guanosine at the 8 position, 8-S-L-cysteinylguanosine. The reaction was accelerated under mildly basic conditions. The cysteine adduct of guanosine was fairly stable and decomposed with a half-life of 193 h at pH 7.4 and 37 °C. Similar results were observed for incubation of 8-bromo-2'-deoxyguanosine with cysteine. The results suggest that 8-bromoguanine in nucleosides, nucleotides, RNA, and DNA can react with thiols resulting in stable adducts.

Ozone (O(3)), a major component of photochemical oxidants, is used recently as a deodorizer in living spaces. It has been reported that O(3) can directly react with DNA, causing mutagenesis in human cells and carcinogenesis in mice. However, little is known about the effects of coexistent ions in the reaction of O(3). In the present study, we analyzed the effects of halides on the reaction of O(3) with nucleosides using reversed-phase high-performance liquid chromatography with ultraviolet detection. When aqueous O(3) solution was added to a nucleoside mixture in potassium phosphate buffer (pH 7.3), the nucleosides were consumed with the following decreasing order of importance: dGuo > Thd > dCyd > dAdo. The effects of addition of fluoride and chloride in the system were slight. Bromide suppressed the reactions of dGuo, Thd, and dAdo but enhanced the reaction of dCyd. The major products were 5-hydroxy-2'-deoxycytidine, 5-bromo-2'-deoxycytidine, and 8-bromo-2'-deoxyguanosine. The time course and pH dependence of the product yield indicated formation of hypobromous acid as the reactive agent. Iodide suppressed all the reactions effectively. The results suggest that bromide may alter the mutation spectrum by O(3) in humans.