Abstract:
In the present study, we investigated the genotoxicity of the active products formed from N-nitrosoproline (NPRO) dissolved in oleic acid following ultraviolet A (UVA) irradiation, bypassing the need for metabolic activation. We previously demonstrated the photomutagenicity of NPRO dissolved in a phosphate-buffered solution. It has been suggested that the association of the nitrosamine group with acid ions facilitates rapid photodissociation and photoactivation. We hypothesized that NPRO\'s inherent carboxyl group may mimic an acid, inducing photodissociation and photomutagenicity, even in a non-aqueous solvent lacking acidic ions. Following UVA irradiation, NPRO dissolved in oleic acid exhibited a dose-dependent mutagenic activity. Similar results were obtained when NPRO was dissolved in linoleic acid and triolein. Nitric oxide formation, which is dependent on NPRO concentration, is accompanied by mutagenic activity. The mutagenicity spectrum obtained in response to NPRO irradiation followed the absorption curve of NPRO dissolved in oleic acid. Irradiated NPRO in oleic acid displayed relative stability, retaining approximately 18, 36, and 63 % of initial mutagenicity after 10 days of storage at 25, 4, and -20 °C, respectively. Thus NPRO stored in a fatty environment undergoes photoactivation upon irradiation, leading to genotoxicity.
摘要:
在本研究中,我们研究了紫外线A(UVA)照射后溶解在油酸中的N-亚硝基脯氨酸(NPRO)形成的活性产物的遗传毒性,绕过代谢激活的需要。我们先前证明了溶解在磷酸盐缓冲溶液中的NPRO的光诱变性。已经提出亚硝胺基团与酸性离子的缔合促进快速光解离和光活化。我们假设NPRO的固有羧基可以模拟酸,诱导光解离和光致突变,即使在缺乏酸性离子的非水溶剂中。UVA照射后,溶解在油酸中的NPRO表现出剂量依赖性诱变活性。当NPRO溶解在亚油酸和三油酸甘油酯中时,获得类似的结果。一氧化氮的形成,这取决于NPRO浓度,伴随着诱变活性。响应于NPRO辐照获得的诱变谱遵循NPRO溶解在油酸中的吸收曲线。辐照的NPRO在油酸中显示出相对稳定性,在25、4和-20°C下储存10天后,保留约18、36和63%的初始诱变性,分别。因此,储存在脂肪性环境中的NPRO在照射时会经历光活化,导致遗传毒性。