Human fecal water modifies adhesion of intestinal bacteria to Caco-2 cells.

The aqueous phase of feces (fecal water) has been suggested to mediate the effects of diet on colon carcinogenesis. We determined whether human fecal water samples, of varying genotoxic potential, had the capacity to alter adhesion of intestinal bacteria to intestinal (Caco-2) cells. Genotoxicity of fecal water samples was measured using the single-cell gel electrophoresis assay ("comet" assay), and bacterial adhesion was measured using a well-established model system. Fecal water genotoxicity was found to correlate positively with inhibition of adhesion of Escherichia coli strains, Salmonella species, and Enterococcus faecium to Caco-2 cells. The presence of fecal water samples did not interfere with adhesion of Bacteroides and Lactobacillus species. Inhibition of adhesion by fecal water was not due to cytotoxicity to Caco-2 cells as cytotoxicities of most fecal water samples were similar, nor was the inhibitory effect due to bacteriotoxicity as toxicity of fecal waters in the 10 strains of bacteria studied was not detected. Results indicate that components in fecal water may alter adhesion of intestinal bacteria to intestinal cell surfaces and that this effect may be correlated to the genotoxic potential of fecal water. This may have consequences for dietary effects on colon carcinogenesis.

Toxicological characterization of a novel in vivo benzo[a]pyrene metabolite, 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid anhydride.

Recently, we described a new in vivo pathway in the metabolism of benzo[a]pyrene (BP) that involves an opening of the aromatic ring system. One of the products of this pathway, isolated from rat urine, was the anhydride of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid (ABADA). We have now investigated the effect of ABADA on several cellular targets, known to be important in tumor formation. ABADA was as efficient as BP-7,8-diol-9,10-epoxide in inducing direct strand breaks but not alkali labile sites in DNA in HT-29 cells and exhibited weak mutagenic activity in Salmonella typhimurium strain TA 102. The cytotoxicity of ABADA to HCT 116 cells appeared to be due to apoptosis, as caspase-3 activity and poly-ADP-ribose polymerase (PARP) cleavage was observed. COX-2 promoter activity was induced by ABADA in HCT 116 cells. In conclusion, this novel metabolic pathway may also be contributing to the carcinogenicity of BP.