Document Detail

Lack of effect of retinoic acid and fluocinolone acetonide on mirex tumor promotion indicates a novel mirex mechanism.
MedLine Citation:
PMID:  7554075     Owner:  NLM     Status:  MEDLINE    
Mirex, a halogenated hydrocarbon, is a potent skin tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. In the present study retinoic acid (RA) and fluocinolone acetonide (FA), classical inhibitors of phorbol ester- and non-phorbol ester-type skin tumor promoters, were examined for their ability to inhibit mirex tumor promotion. Female CD-1 mice were initiated with 200 nmol DMBA and promoted with equipotent promoting doses of either 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) or 200 nmol mirex twice weekly for 25 weeks and RA (2(1 or 5 nmol), FA (0.5 or 2 nmol) or acetone were applied 30 min prior to each TPA or mirex dose. TPA-promoted papilloma formation was strongly inhibited by > 70% with both doses of RA and by > 90% with both doses of FA. In contrast, mirex-promoted papilloma formation was not inhibited by either dose of RA or 0.5 nmol FA and 2 nmol FA weakly inhibited mirex-promoted papillomas by only 32%. TPA- and mirex-promoted papillomas that were refractory to RA and FA demonstrated the same incidence of Ha-ras mutation as TPA- or mirex-promoted papillomas without RA and FA treatment, further indicating that the inhibitory activity of RA and FA is promoter-dependent and not solely dependent on mutant Ha-ras. FA (2 nmol) treatment completely abolished TPA-induced epidermal hyperplasia and proliferating cell nuclear antigen (PCNA) S phase-positive cells, however, FA had no inhibitory effect on the weak proliferative response induced by mirex. Collectively, these results indicate that the promotional activity of mirex, as well as its weak proliferative response, result from a distinct promoter mechanism and/or that mirex promotes a unique population of epidermal cells that are insensitive to FA and RA and cannot be distinguished by their mutant Ha-ras genotype.
T W Kim; R C Smart
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  16     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-11-20     Completed Date:  1995-11-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2199-204     Citation Subset:  IM    
Department of Toxicology, North Carolina State University, Raleigh 27695-7633, USA.
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MeSH Terms
9,10-Dimethyl-1,2-benzanthracene / toxicity
Anticarcinogenic Agents / therapeutic use*
Base Sequence
Carcinogens / toxicity*
Cell Division / drug effects
Drug Interactions
Ear, External / drug effects
Edema / chemically induced,  drug therapy
Fluocinolone Acetonide / therapeutic use*
Genes, ras / drug effects
Mice, Inbred Strains
Mirex / antagonists & inhibitors,  toxicity*
Molecular Sequence Data
Papilloma / chemically induced,  prevention & control
Skin Neoplasms / chemically induced,  prevention & control
Tetradecanoylphorbol Acetate / toxicity
Tretinoin / therapeutic use*
Grant Support
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Carcinogens; 16561-29-8/Tetradecanoylphorbol Acetate; 2385-85-5/Mirex; 302-79-4/Tretinoin; 57-97-6/9,10-Dimethyl-1,2-benzanthracene; 67-73-2/Fluocinolone Acetonide

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