Fecapentaenes are direct-acting human fecal mutagens and are therefore potential candidates as human colon carcinogens. Several in vitro studies by other investigators have demonstrated potent mutagenic effects of fecapentaene-12 (FP-12) in bacterial cells, low cell transforming activity in vitro and mammalian mutagenic activity. The chemical purity and stability of FP-12 was determined to develop effective handling procedures during rodent exposure. Maintenance under argon in DMS0, and with added Vitamin E, proved useful. The diacetate of FP-12 was also synthesized. Rodent carcinogenesis experiments were carried out to determine potential carcinogenic activity. Skin painting studies in SENCAR mice showed lack of tumor-initiating activity, complete carcinogenesis or tumor-promoting activity in three separate experiments, some of which were repeated to conclusively demonstrate the negative findings. Intrarectal and subcutaneous administration to mice and rats have not provided convincing evidence of the carcinogenesis of FP-12. Total doses of up to 16 mg of FP-12 were used. The limitation of these in vivo assays involved the potentially low total doses utilized. FP-12 was mutagenic in vivo in rats by the subcutaneous granuloma pouch assay, but no tumors developed. Our studies provide no evidence for the carcinogenicity of FP-12, although a weak carcinogenic effect has not been eliminated.
