PMID- 3135955 OWN - NLM STAT- MEDLINE DCOM- 19880909 LR - 20190510 IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 9 IP - 8 DP - 1988 Aug TI - Modulation of chrysarobin skin tumor promotion. PG - 1445-50 AB - The present study examined the effect of several prototypic inhibitors of phorbol ester skin tumor promotion on skin tumor promotion by chrysarobin, an anthrone tumor promoter. Retinoic acid (RA) inhibited skin tumor promotion by chrysarobin; however, the degree of inhibition was dependent on the treatment protocol. When RA (10 micrograms/mouse) was given 1 h after each twice-weekly application of chrysarobin (220 nmol/mouse), a marked inhibition of papilloma formation was observed (78%). In additional experiments, using a once-weekly application of chrysarobin, RA also inhibited skin tumor promotion but the magnitude of inhibition was less. Interestingly, RA (10 micrograms/mouse), given 1 or 6 h after the promoter, did not inhibit the induction of epidermal ornithine decarboxylase (ODC) activity induced by a single topical application of chrysarobin (220 nmol). Fluocinolone acetonide (1 microgram/mouse), given 5 min before each twice-weekly application of chrysarobin (220 nmol/mouse) effectively inhibited skin tumor promotion (88%). A 0.5 or 0.25% supplement of alpha-difluoromethylornithine (alpha-DFMO) in the drinking water inhibited the induction of epidermal ODC following chrysarobin (220 nmol/mouse) treatment by 85 or 70%, respectively. Supplements of both 0.25 and 0.5% of alpha-DFMO also led to a 50 and 61% inhibition, respectively, in the number of papillomas per mouse after 25 weeks of promotion with chrysarobin. Interestingly, 0.25% alpha-DFMO in the drinking water did not reduce the number of papillomas per mouse after 20 weeks of promotion with 1.7 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the number of papillomas per mouse that were greater than or equal to 4 mm in diameter was significantly reduced in both chrysarobin- and TPA-treated mice. The data indicate that RA, FA and alpha-DFMO may be general inhibitors of tumor promoter regardless of the chemical class of tumor promoter. The ability of these inhibitors of phorbol ester promotion to inhibit anthrone promotion indicates that some common biochemical pathways may exist for both classes of skin tumor promoters. FAU - DiGiovanni, J AU - DiGiovanni J AD - University of Texas System Cancer Center, Smithville 78957. FAU - Kruszewski, F H AU - Kruszewski FH FAU - Chenicek, K J AU - Chenicek KJ LA - eng GR - CA 37111/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Anthracenes) RN - 0 (Carcinogens) RN - 0CD5FD6S2M (Fluocinolone Acetonide) RN - 5688UTC01R (Tretinoin) RN - 6307EF51M1 (chrysarobin) RN - EC 4.1.1.17 (Ornithine Decarboxylase) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - ZQN1G5V6SR (Eflornithine) SB - IM MH - Animals MH - Anthracenes/*toxicity MH - *Carcinogens MH - Cocarcinogenesis MH - Eflornithine/pharmacology MH - Female MH - Fluocinolone Acetonide/pharmacology MH - Mice MH - Ornithine Decarboxylase/biosynthesis MH - Papilloma/chemically induced MH - Skin/enzymology MH - Skin Neoplasms/*chemically induced/prevention & control MH - Tetradecanoylphorbol Acetate MH - Tretinoin/pharmacology EDAT- 1988/08/01 00:00 MHDA- 1988/08/01 00:01 CRDT- 1988/08/01 00:00 PHST- 1988/08/01 00:00 [pubmed] PHST- 1988/08/01 00:01 [medline] PHST- 1988/08/01 00:00 [entrez] AID - 10.1093/carcin/9.8.1445 [doi] PST - ppublish SO - Carcinogenesis. 1988 Aug;9(8):1445-50. doi: 10.1093/carcin/9.8.1445.