Inhibition of 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation in mice by dehydroepiandrosterone and two synthetic analogs.
Previous work has demonstrated that the adrenal steroid, dehydroepiandrosterone (3-beta-hydroxy-5-androsten-17-one, DHEA), has broad spectrum tumor chemopreventive activity in laboratory mice and rats, inhibiting the development of spontaneous breast cancer and chemically induced tumors of the lung, colon, skin, thyroid and liver. DHEA treatment produces specific side-effects, including estrogenic and androgenic action and an increase in liver weight, which could limit its use as a cancer chemopreventive drug. It is now shown that oral administration of the synthetic steroid 16 alpha-fluoro-5-androsten-17-one, which lacks the side-effects of DHEA treatment, to CD-1 mice inhibits 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation at both the initiation and promotion stage. The synthetic steroid is more potent as an inhibitor of papilloma formation than comparably administered DHEA.
Schwartz
A G
AG
Fels Research Institute, Temple University Medical School, Philadelphia, PA 19140.
Fairman
D K
DK
Polansky
M
M
Lewbart
M L
ML
Pashko
L L
LL
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents; D001835:Body Weight / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D003687:Dehydroepiandrosterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate