Inhibition of 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor formation in mice by 16α-fluoro-5-androsten-17-one and its reversal by deoxyribonucleosides
| Autor: | Arthur G. Schwartz, Lewbart Marvin Louis, Laura L. Pashko |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Cancer Research
medicine.medical_specialty Skin Neoplasms DMBA Dehydroepiandrosterone Deoxyribonucleosides Mice Inbred Strains Pharmacology 12-O-Tetradecanoylphorbol-13-acetate Mice chemistry.chemical_compound Deoxyribonucleotide Internal medicine Animals Medicine Deoxyguanosine Drug Interactions Anticarcinogen Papilloma business.industry Body Weight General Medicine Endocrinology chemistry Tetradecanoylphorbol Acetate Androstenes Female Tumor promotion business |
| Zdroj: | Carcinogenesis. 12:2189-2192 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/12.11.2189 |
| Popis: | The work of ourselves and others has demonstrated that dehydroepiandrosterone (DHEA) dispalys a broad spectrum of cancer preventive action in laboratory rodents, with little toxicity. In the two-stage skin tumorigenesis model in mice, topical application of the synthetic DHEA analog 16 alpha-fluoro-5-androsten-17-one, a more potent preventive agent than DHEA without the sex-hormonal side-effects of the parent steroid, markedly inhibited promotion of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumor development by 12-O-tetradecanoylphorbol-13-acetate (TPA). DHEA is a powerful inhibitor of glucose-6-phosphate dehydrogenase (G6PDH), suggesting that its inhibiting effect in carcinogenesis may be due to a lack of NADPH and ribose-5-phosphate production for deoxyribonucleotide synthesis and subsequent DNA replication. Further evidence of a reduced NADPH and ribose-5-phosphate pool on the lowering of intracellular deoxyribonucleotide levels has been demonstrated in this paper by completely reversing the 16 alpha-fluoro-5-androsten-17-one-induced inhibition of tumor promotion by the addition of the four deoxyribonucleosides-deoxyadenosine, deoxycytidine, deoxyguanosine and thymidine--to the drinking water during the promotion period of tumorigenesis. |
| Databáze: | OpenAIRE |
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