UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

Mutagenicity and NO Formation from UVA Irradiated N-Nitrosoproline, and Characterization of Photoproduct Formed in UVA-irradiated Mixture of N-Nitrosoproline with 2^|^prime;-Deoxyguanosine in Neutral Solution

“…al sunlight was su‹cient to photolyze N-nitrosodialkylamines (16,22,23). The present results show that photoreaction of NPRO with dG produced 8-oxodG in aqueous solution at pH 7.4. dG exhibits the lowest oxidation potential of the deoxynucleotides, and consequently the oxidation of DNA eventually leads to the formation of oxidative products of dG (5,26).…”

“…The product in the peak (hereafter referred to as N1) was chromatographically identical to that of an authentic specimen of 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxodG). In our previous work (22,23), we observed formation of 8-oxodG in calf thymus DNA treated with N-dialkylnitrosamines plus UVA in sodium phosphate buŠer (20 mM, pH 7.4). Thus, photoproduct N1 from dG was identiˆed as 8-oxodG (Fig.…”

The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation

“…NDMA, NDPA, and NEMA increased the TA100 revertant in the presence of S 9 , suggesting they are indirect mutagens (i.e., require metabolism) giving rise to base-pair substitutions [83]. The S 9 -mix at 1000-fold doubled the frequency of the TA100 revertant.…”

Photogenotoxicity and Photomutagenicity of Medicines, Carcinogens and Endogenous Compounds

“…It was thought that nitrosamine itself was an inert solvent, and that the metabolites of nitrosamine were responsible for the toxic eŠects (43,44). With simultaneous irradiation of UVA, photomutagenic eŠects of N-dialkylnitrosamines were observed in Ames bacteria (S. typhimurium TA1535) in the absence of metabolic activation (45,46). The Ndialkylnitrosamines produced strand breaks in treated DNA in the presence of UVA.…”

“…The plots of mutation frequency and NO formation aligned with the absorption curve of N-nitrosamine, indicating that nitrosamine acts as a sensitizer of UVA. The proposed hypothesis involves the absorption of UVA photons by the N-nitroso moiety of N-dialkylnitrosamines, UVA-photolysis of N-dialkylnitrosamines to release nitric oxide, and subsequent production of alkyl radical cations and active oxygen species which cause DNA strand breaks, oxidative and alkylative DNA damage, and mutations (45,46).…”