Stability of fecapentaene-12 and its carcinogenicity in F-344 rats.
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).
Shamsuddin
A M
AM
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Ullah
A
A
Baten
A
A
Hale
E
E
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004355:Drug Stability; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D011090:Polyenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013050:Spectrometry, Fluorescence / Q000379:methods
D009153:Mutagens; D011090:Polyenes; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene; D004247:DNA