Photolysis of three antiviral drugs acyclovir, zidovudine and lamivudine in surface freshwater and seawater.

Photodegradation is an important elimination process for many pharmaceuticals in surface waters. In this study, photodegradation of three antiviral drugs, acyclovir, zidovudine, and lamivudine, was investigated in pure water, freshwater, and seawater under the irradiation of simulated sunlight. Results showed that zidovudine was easily transformed via direct photolysis, while acyclovir and lamivudine were mainly transformed via indirect photolysis. We found that in freshwater, nitrate enhanced the photodegradation of the three antiviral drugs, bicarbonate promoted the photodegradation of acyclovir, and dissolved organic matter (DOM) accelerated the photolysis of acyclovir and lamivudine. In seawater, the photolysis of acyclovir was not susceptible to Cl(-), Br(-) and ionic strength; however, the photolysis of zidovudine was inhibited by Cl(-) and Br(-), and the photolysis of lamivudine was enhanced by Cl(-), Br(-) and ionic strength. Second-order reaction rate constants for the three antiviral drugs with (1)O2 (k1O2) and OH (kOH) were also measured. These results are important for fate and ecological risk assessment of the antiviral drugs in natural waters.

Oxidative DNA damage induced by photodegradation products of 3(')-azido-3(')-deoxythymidine.

3(')-Azido-3(')-deoxythymidine (AZT) is carcinogenic to experimental animals and can cause the formation of 8-oxo-7,8-dihydro-2(')-deoxyguanosine (8-oxodG) in humans and animals. To clarify the mechanism of carcinogenesis by AZT, we investigated DNA damage induced by its photodegradation products, using 32P-5(')-end-labeled DNA fragments obtained from human genes. Following exposure to UVB, AZT induced DNA damage in the presence of Cu(II). Catalase inhibited DNA damage, indicating the involvement of H(2)O(2). UVB-exposed AZT plus Cu(II) induced 8-oxodG formation in a dose-dependent manner. Mass spectrum of UVB-exposed AZT demonstrated the generation of a hydroxylamine derivative. The colorimetric determination suggested that AZT was converted into the hydroxylamine derivative depending on UVB doses. UVB-exposed AZT induced double base damage at the 5(')-ACG-3(') sequence, complementary to a hot spot of the p53 gene. The basic compound, hydroxylamine, showed similar site specificity. The hydroxylamine derivative produced by photodegradation and/or possible metabolism of AZT induces oxidative DNA damage, which may participate in carcinogenesis.