Stability of fecapentaene-12 and its carcinogenicity in F-344 rats

Abstract

Carcinogenicity studies of the fecal mutagen fecapentaene-12 (FP-12) have been hampered because of its apparent instability. We report here that: (i) contrary to the popular belief, FP-12 is quite stable, particularly at micromolar to nanomolar concentration; and (ii) its characteristic spectrophotometric absorbance spectrum is a function of the solvent or vehicle. Using synchronous fluorescence spectrophotometry (SFS), we have determined that at delta lambda 36.5 nm FP-12 gives a characteristic single emission peak between 413 and 423 nm, allowing us to identify FP-12 in DNA when reacted in vitro. We also report an increased incidence (statistically not significant) of fibrosarcomas and mammary carcinomas in male F-344 rats following intrarectal instillation of FP-12. In the in vitro human colon explant model, direct addition of FP-12 results in alteration in mucin histochemical changes typical of precancer and cancer. Our results support the contention that FP-12 is a naturally occurring carcinogen and may be responsible for human cancer(s).