Fecal mutagen fecapentaene-12 damages mammalian colon epithelial DNA.

Abstract

Fecapentaenes are fecal mutagens that are naturally produced in the human colon and have been shown to be highly mutagenic in the Ames assay system. However to date no studies have been reported regarding the effects of fecapentaene in the target epithelium. In vivo studies with fecapentaene-12 (FP-12) using Fischer 344 rats in our laboratory indicate that a concentration of 10(-6) M FP-12 is capable of inducing a 2.7-fold increase (P less than 0.001) in [3H]-thymidine incorporation into DNA. Autoradiographic studies demonstrate a similar (2.6-fold) increase in the labelling index but an 8.8-fold reduction in the mitotic rate in colonic epithelial cells. Results of DNA single-strand breakage measurements show that in vivo treatment with FP-12 at concentrations of 1 microM introduces a 16-fold increase (P less than 0.001) in the number of alkali-labile sites over controls. Similar studies in in vitro assays indicate a linear trend in the number of alkali-labile sites over a range of concentrations varying from 1 nM to 1 microM. These findings indicate that the fecal mutagen FP-12 induces damage in situ to nucleic acids and thus may play a role in neoplastic transformation of the colon.