RESUMEN
The concentration of N-nitrosamines (N-nitrosodimethylamine and N-nitrosodiethylamine) was measured in blood samples from children after consumption of drinking water with high content of nitrates (main group) or water meeting health standards (reference group). N-nitrosodimethylamine level in the blood from children of the main group differed from that in the reference group by 2.6 times (0.00026±0.00012 and 0.0001±0.00092 mg/dm3, respectively; p<0.05). The specific immune response to N-nitrosodimethylamine exposure was manifested in an increase in the level of specific serum IgG (2 times higher than that in the reference group). An increase in the specific sensitivity to N-nitrosodimethylamine (by the criterion of IgG) was observed in 60.7% subjects. A correlation was found between an increase in the level of IgG to N-nitrosodimethylamine and rise in the concentration of N-nitrosodimethylamine in the blood (R 2 =0.35; p=0.021). Under these conditions the spontaneous and induced production of arachidonic acid metabolites (leukotrienes) increased by 2.1 times, while the expression of p53 transcription factor (responsible for oncosuppression) decreased by 1.9 times as compared to those in the reference group (p<0.05).
Asunto(s)
Dietilnitrosamina/sangre , Dimetilnitrosamina/sangre , Sistema Inmunológico/efectos de los fármacos , Inmunoglobulina G/biosíntesis , Nitratos/sangre , Estudios de Casos y Controles , Niño , Preescolar , Dietilnitrosamina/inmunología , Dimetilnitrosamina/inmunología , Agua Potable/química , Femenino , Regulación de la Expresión Génica , Humanos , Leucotrienos/agonistas , Leucotrienos/sangre , Leucotrienos/inmunología , Masculino , Nitratos/administración & dosificación , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/sangre , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/inmunologíaRESUMEN
Respiratory epithelial cells are known to contribute to immune responses through the release of mediators. The aim of this study was to characterize the immunomodulatory effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco carcinogen, on respiratory epithelial cells and to compare two metabolic pathways, alpha-methylhydroxylation and alpha-methylenehydroxylation, involved in these effects using selective precursors, 4-(acetoxy-methylnitrosamino)-1-(3-pyridil)-1-butanone (NNKOAc) and N-nitroso (acetoxymethyl) methylamine (NDMAOAc), respectively. Human bronchial and alveolar epithelial cell lines, BEAS-2B and A549, respectively, were treated with NNK, NNKOAc and NDMAOAc for 24 h with and without tumour necrosis factor (TNF) and mediators released in cell-free supernatants were measured by enzyme-linked immunosorbent assay (ELISA). NNK significantly inhibited interleukin (IL)-8, IL-6 and monocyte chemoattractant protein-1 (MCP-1) production in both cell types. Similar results were observed with primary bronchial and alveolar epithelial cells. Although NNK increased prostaglandin E(2) (PGE(2)) production by A549 cells, its immunomodulatory effects were not mediated by PGE(2) according to the results with cyclo-oxygenase inhibitors. NNKOAc mimicked NNK effects, whereas NDMAOAc significantly inhibited IL-8 production in BEAS-2B cells and MCP-1 in both cell types. These results demonstrate that NNK and its reactive metabolites have immunosuppressive effects on respiratory epithelial cells, which could contribute to the increased respiratory infections observed in smokers and the development and/or the progression of lung cancer.
Asunto(s)
Bronquios/inmunología , Carcinógenos/farmacología , Citocinas/inmunología , Dimetilnitrosamina/análogos & derivados , Nitrosaminas/inmunología , Alveolos Pulmonares/inmunología , Línea Celular , Quimiocina CCL2/inmunología , Dimetilnitrosamina/inmunología , Dimetilnitrosamina/farmacología , Dinoprostona/biosíntesis , Dinoprostona/inmunología , Células Epiteliales/inmunología , Humanos , Hidroxilación , Interleucina-6/inmunología , Interleucina-8/inmunología , Nitrosaminas/farmacología , Piridinas/inmunología , Piridinas/farmacologíaAsunto(s)
Formación de Anticuerpos/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Sistema Inmunológico/efectos de los fármacos , Animales , Arocloros/inmunología , Arocloros/farmacología , Cadmio/inmunología , Cadmio/farmacología , Dimetilnitrosamina/inmunología , Dimetilnitrosamina/farmacología , Interleucina-2/biosíntesis , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Plomo/inmunología , Plomo/farmacología , Activación de Linfocitos/efectos de los fármacos , Bifenilos Policlorados/farmacología , Ratas , Linfocitos T/efectos de los fármacos , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
The antigenic structure of the livers of mice and rats after a single hepatocarcinogenic treatment was investigated using the immunodiffuse and immunofluorescent methods. The next day after carcinogen application changes characteristic of hepatocellular tumors were observed: decrease in the synthesis of organospecific antigens and intensification of the synthesis of heteroorganic antigens.