In vivo and in vitro genotoxicity of N-nitrosopyrrolidine following UVA irradiation.

Abstract

N-nitrosopyrrolidine (NPYR) is a volatile nitrosamine that is thought to be a human carcinogen. It is found in air, wastewater, food, and feed. Photo-activation of NPYR can occur as it drifts through the environment. We previously found that NPYR irradiated in phosphate buffer was directly mutagenic without metabolic activation or simultaneous irradiation. Here, we aimed to determine NPYR activity after UVA irradiation. The mutagenic activity of irradiated NPYR was relatively stable, and ~ 23% of it persisted after 168 h of storage at 37 °C. Micronuclei (MN) were also found without metabolic activation in human-derived keratinocytes (HaCaT cells) after NPYR irradiation in vitro and the peripheral blood reticulocytes (PBRs) of mice with inhibited cytochrome-P450-mediated metabolism then injected with irradiated NPYR in vivo. The active photoproduct of NPYR is thought to be genotoxic to bone marrow, resulting in MN formation in PBRs. The action spectrum of MN formation in PBRs exposed to NPYR irradiated with monochromatic light was plotted along the absorption curve. The production ratio of active NPYR photoproduct followed the NPYR absorption curve. Genotoxicity becomes systemic with externally irradiated NPYR that penetrates the skin or when NPYR is irradiated just under the skin and enters the systemic circulation. Risk analyses of public health-related volatile N-nitrosamines generated via environmental photoactivation including NPYR, should be considered.