Studies were conducted for investigation of the inhibitory effect on the development of experimental
tumors of the skin and liver with
vitamin A-like compounds, with a particular focus on a new synthetic derivative of the
polyprenoic acid 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166). Incidence of skin
papilloma, chemically induced in mice, was significantly influenced by dietary
vitamin A contents. When given orally at a dose of 200 mg/kg
body weight,
beta-carotene regressed the skin
papilloma to some extent (-16% at 14 days), although its effect was much weaker than that of E-5166 (-43%). E-5166 also significantly reduced
tumor incidences of
experimental hepatomas induced by chemical
carcinogen in rats as well as in "spontaneous"
hepatoma-bearing mice (C3H/HeNCrj) genetically determined. Further chemical studies revealed that
retinol was locally deficient in the
hepatomas but not in adjacent normal livers: In particular,
anhydroretinol was newly detected in the
tumors of spontaneous
hepatoma-bearing mice, suggesting increased conversion of
retinol into the inactive metabolite. Moreover, cellular
retinoid-binding protein, F-type (an oncofetal
protein), also newly appeared exclusively in the
hepatoma tissues, suggesting that the preventive effect of E-5166 on hepatocarcinogenesis was mediated, at least in part, through its binding with the new
retinoid receptor.