Modulation of genotoxic responses by environmental agents.

A metabolite of a widely used pesticide, paraoxon, exerted a dramatic mutagenic synergistic effect in Salmonella typhimurium with a number of mammalian-activated or plant-activated aromatic amines and heterocyclic amines. The mutagenic synergy required an activated an aromatic amine, and was not attributable to the generation of new mutagenic products or to the modification of the stability of the activated aromatic amine products. Paraoxon modulated the genotoxic potency of dietaiy heterocyclic amines in human cells. The results of this study raise the concern of the environmental effects of organophosphorus ester insecticides. A clone of the Chinese hamster ovary cell line, AS52, was isolated, characterised and analysed under identical treatment conditions with the mutagens 2-acetoxy-acetylaminofluorene (2AAAF), ethyl methanesulphonate (EMS), and UV radiation. The genetic endpoints included acute DNA damage detected in the alkaline single cell gel electrophoresis (SCGE) assay, whole cell clastogenicity detected with laser beam flow cytometry and forward mutation at a target gene. There were statistically significant increases in DNA damage and forward mutation with all three mutagens. Statistically significant increases in chromosome damage were observed with 2AAAF and EMS but not with UV. A non-uniform distribution of DNA damage throughout the genome was indicated with the chemical mutagens in the SCGE assay. Another type of modulation in genotoxic response was investigated whereby numerous commercial soybean processing products and by-products were analysed for their antimutagenic and antigenotoxic activities. Antimutagenic activity was detected in a soybean processing by-product, soybean molasses and in an ethanol extract, fraction PCC. PCC protected mammalian cells against direct DNA damage, clastogenic damage and point mutation induced by 2AAAF. A fraction of PCC, PCC100 was an effective antimutagen in mammalian cells and in human lymphocytes. Analytical chemical studies identified the compounds responsible for the antimutagenic activity as the soyasaponins I, III and V