The topic of the present study is the establishment of experimental model systems for the study of human colon cancer which may have been caused by genotoxic compunds produced from the natural diet. Fecapentaene-12 (fec-12), which has been recently reported to the account for mutagenicity in human fecal extracts is investigated extensively for its cellular and molecular interactions associated with its carcinogenic potentials. The mutagenicity of fec-12 is assayed with Salmonella TA104, TA100, and TA98. Fec-12 is highly mutagenic to TA100 and TA104 without metabolic activitation. To investigate the molecular mechanisms of mutation, the plasmid mediated mutation assay, which was esablished in our laboratory, was utilized. Fec-12 is highly cytotoxic to normal human fibroblasts and is more potent in DNA repair deficient (XP) strains. Fec-12 is also mutagenic to both normal and XP cells inducing up to a 10-fold increase in 6-thioguanine resistant mutants. The interaction of fec-12 with plasmid DNA is investigated by denaturation-renaturation kinetics and electron microscopy. The damage and repair of the DNA are studied by the alkaline elution techniques with fec-12 treated human fibroblasts. These studies indicate that the genotoxicity and mutation may be mediated by cross-linking and strand breaks of the DNA induced by fec-12.
