TY - JOUR
T1 - Inhibition of phorbol ester-induced tumor promotion in mice by vitamin a analog and anti-inflammatory steroid
AU - Weeks, C. E.
AU - Slaga, T. J.
AU - Hennings, H.
AU - Gleason, G. L.
AU - Bracken, W. M.
N1 - Funding Information:
1 Received July 18, 1978; accepted January 17, 1979. 2 Research sponsored by the Division of Biomedical and Environmental Research, U.S. Department of Energy, under contract W-7405-eng-26 with the Union Carbide Corp. 3 Biology Division, Oak Ridge National Laboratory, P.O. Box Y, Oak Ridge, Tenn. 37830. 4 Experimental Pathology Branch, Division of Cancer Cause and Prevention, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20205.
PY - 1979/8
Y1 - 1979/8
N2 - The effects of a vitamin A analog, TMMP ethyl retlnoate [or ethyl-9-(4-methoxy-2,3,6-trlmethylphenyl)-3,7-dlmeth- yl-frsns-2,4,6,8-nonatetraenoate] (abbreviated Ro 10–9359), and an antl-lnflammatory steroid, fluoclnolone acetonlde (or 6α,9α- dlfluoro-11β,16α,17,21-tetrahydroxypregna-1,4-dlene-3,20-dlone cyclic 16,17-acetal) (abbreviated FA), given alone or together were studied In a two-stage carcinogenesis system. The phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) was used as the tumor promoter In a 7,12-d!methylbenz[a]anthracene (DMBA)-lnltlated mouse skin system. Two stocks of female mice, CD®-1 and Senear, which differ in their degrees of sensitivity to skin carcinogenesis, were used. A dose-dependent inhibition of carcinogenic expression, as determined by a decreased number of papillomas per animal, was observed in each mouse stock with the use of both FA and Ro 10–9359 when given alone. When FA and Ro 10–9359 were given together, an enhanced effect on the lowering of tumor Incidence was noted. FA effectively Inhibited tumor formation in the sensitive mouse stock even when the steroid was given 1 day prior to TPA treatment under conditions of unusually high doses of Initiator (DMBA) and/or promoter (TPA). These results suggest that both antl-lnflammatory steroids and retinoids Inhibit tumor promotion and can be effectively used as a combination regimen for Increased chemopreventive response.
AB - The effects of a vitamin A analog, TMMP ethyl retlnoate [or ethyl-9-(4-methoxy-2,3,6-trlmethylphenyl)-3,7-dlmeth- yl-frsns-2,4,6,8-nonatetraenoate] (abbreviated Ro 10–9359), and an antl-lnflammatory steroid, fluoclnolone acetonlde (or 6α,9α- dlfluoro-11β,16α,17,21-tetrahydroxypregna-1,4-dlene-3,20-dlone cyclic 16,17-acetal) (abbreviated FA), given alone or together were studied In a two-stage carcinogenesis system. The phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) was used as the tumor promoter In a 7,12-d!methylbenz[a]anthracene (DMBA)-lnltlated mouse skin system. Two stocks of female mice, CD®-1 and Senear, which differ in their degrees of sensitivity to skin carcinogenesis, were used. A dose-dependent inhibition of carcinogenic expression, as determined by a decreased number of papillomas per animal, was observed in each mouse stock with the use of both FA and Ro 10–9359 when given alone. When FA and Ro 10–9359 were given together, an enhanced effect on the lowering of tumor Incidence was noted. FA effectively Inhibited tumor formation in the sensitive mouse stock even when the steroid was given 1 day prior to TPA treatment under conditions of unusually high doses of Initiator (DMBA) and/or promoter (TPA). These results suggest that both antl-lnflammatory steroids and retinoids Inhibit tumor promotion and can be effectively used as a combination regimen for Increased chemopreventive response.
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U2 - 10.1093/jnci/63.2.401
DO - 10.1093/jnci/63.2.401
M3 - Article
C2 - 110970
AN - SCOPUS:0018688642
VL - 63
SP - 401
EP - 406
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 2
ER -