Prevention of genotoxic effects by dietary constituents in various organs of mice treated with nitrosamines.

Abstract

In recent years, numerous compounds have been identified that exert antimutagenic effects toward nitrosamines in vitro, but it is unknown at present if they are also active under in vivo conditions (1). In addition, it has been shown that certain dietary constituents prevent nitrosamine-induced carcinogenesis in rodents, but it is not yet proven whether these properties are paralleled by prevention of DNA damage (2,3). The aim of the present study was to investigate the inhibitory effects of four representatives of different groups of putative antimutagens or anticarcinogens toward nitrosamine-induced genotoxicity in the living animal. The test system used was the differential DNA repair host mediated assay with Escherichia coli K-12 derivatives. This assay enables the detection of repairable DNA damage in various organs (liver, kidney, lungs, spleen, testes, and blood) of chemically treated mice. In addition, in vitro assays were carried out under comparable experimental conditions using the same indicator strains. Finally, biochemical experiments were conducted aimed at determining the influence of the various compounds on the ahydroxylation of nitrosamines.