Comparison of the inhibitory effects of retinoids on 12- O-tetradecanoylphorbol-13-acetate-promoted tumor formation in CD-1 and Sencar mice

Abstract

Linear regression analysis of the dose levels of retinoids required to inhibit the formation of papillomas by 50% in mouse dorsal epidermis topically treated with 7,12-dimethylbenz[ a]anthracene (DMBA) (200 nmol) and then promoted 2 weeks later with twice-weekly applications of 12- O-tetradecanoylphorbol-13-acetate (TPA) (8.5 nmol) indicated that there was a good correlation ( r = 0.9095, P < 0.02) between retinoid inhibitory activities in the CD-1 mouse at 20 weeks after the start of promotion and in the Sencar mouse after 12 weeks of promotion. The ID 50 values (nmol) determined were as follows: all- trans-retinoic acid (RA) (3.5, CD-1; 17, Sencar); 4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1 E-propen-1-yl]benzoic acid (0.14, CD-1; 0.71, Sencar); 4-[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)- 1 E-propen-2-yl]benzoic acid (0.54, CD-1; 1.9, Sencar); 6-[1-(4-carboxyphenyl)-1 E-propen-2-yl]-3,4- dihydro-4,4-dimethyl-2 H-1-benzothiopyran (3.0 CD-1; 11, Sencar); 7-[1-(4-carboxyphenyl)-1 E-propen-2-yl)-3,4-dihydro- 4,4-dimethyl-2 H-1-benzothiopyran (1.5, CD-1; 0.4, Sencar); 2-[1-(4-carboxyphenyl)-1 E-propen-2-yl]- 4,5,6,7-tetrahydro-4,4-dimethyl-benzo[ b]thiophene (0.30, CD-1; 2.3, Sencar).