Activation of N-nitrosodialkylamines by near-ultraviolet irradiation: formation of directly-acting mutagens and DNA-damaging products.
On near-ultraviolet (UVA) irradiation in a phosphate buffer, N-nitrosomorpholine (NMOR) and N-nitrosopyrrolidine (NPYR) were converted into directly-acting mutagens. The activated NPYR was fractionated, and the active product was isolated. The compound was shown to be identical to alpha-phosphonooxy NPYR on the basis of several properties: retention times in high-performance liquid chromatograms, mutagenic specificity and potency, ultraviolet spectrum, and inactivation by phosphatase treatment. Photoactivation was inhibited by superoxide dismutase, and therefore superoxide is implicated as playing a key role in mutagen formation. N-Nitrosoproline (NPRO) and eighteen other N-nitrosodialkylamines were irradiated with UVA in the presence of phi X174 RFI DNA. The DNA underwent single-strand breaks to give RFII DNA, indicating that N-nitrosodialkylamines in general have this property. DNA chain cleavage was inhibited both by superoxide dismutase and hydroxyl-radical scavengers. These results provide new information on the genotoxic mechanism of action of N-nitrosodialkylamines.
D010584:Bacteriophage phi X 174; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D009152:Mutagenicity Tests; D009242:N-Nitrosopyrrolidine / Q000528:radiation effects; D009602:Nitrosamines / Q000528:radiation effects* / Q000633:toxicity; D014466:Ultraviolet Rays
D004277:DNA, Single-Stranded; D009602:Nitrosamines; C002741:N-nitrosomorpholine; C010259:nitrosoproline; D009242:N-Nitrosopyrrolidine