Mutation induction by reactive nitrogen species and neutrophils in an in vitro/in vivo murine tumour model.

Abstract

Our laboratory has been interested in factors in the tumour microenvironment that may contribute to mutagenesis, and thus lead to tumour progression. The well documented relationship between chronic inflammatory states and cancer implicates inflammatory cells, such as macrophages and neutrophils, and their products as having a role in carcinogenesis. Using the MN-11 system, an in vitro/in vivo murine tumour model developed in our laboratory, the mutagenicity of neutrophils and one of their products, reactive nitrogen species, was studied. To further investigate the mechanism of the observed mutagenicity of nitric oxide donors on MN-11 cells, cellular glutathione levels of cells treated with glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) were manipulated. Reactive nitrogen species, such as nitric oxide, are part of the microbicidal armament of neutrophils. Neutrophils have been implicated as a possible link between chronic inflammation and cancer, and are the most abundant inflammatory cell type observed in MN-11 tumours. Thus, the role that neutrophils have in causing mutations was investigated. (Abstract shortened by UMI.)