Abstract |
The chemopreventive efficacy of N-acetyl-L-cysteine (NAC), anethole trithione, miconazole and phenethylisothiocyanate ( PEITC), each of which would be expected to alter carcinogen metabolism, was examined in the dimethylbenzanthracene (DMBA) mammary carcinogenesis model. In this protocol, animals were exposed to non-toxic doses of the chemopreventives in the diet beginning 7 days prior to DMBA administration and then continuously throughout the duration of the assay (100 days post carcinogen). Miconazole, an antifungal agent with relatively broad inhibitory activity toward a variety of cytochromes P450, increased mammary tumor latency, decreased tumor incidence at the highest dose and decreased tumor multiplicity up to 60%. Anethole trithione, a substituted dithiolthione and an analog of the relatively broad-spectrum chemopreventive oltipraz, was administered in the diet and significantly inhibited mammary cancer multiplicity but not cancer incidence. NAC, an antimucolytic agent, failed to inhibit DMBA-induced mammary tumorigenesis. Surprisingly, treatment with DMBA plus PEITC, a potent inhibitor of cytochrome P450 2E1, actually increased the multiplicity of tumors relative to that observed with DMBA alone.
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Authors | R A Lubet, V E Steele, I Eto, M M Juliana, G J Kelloff, C J Grubbs |
Journal | International journal of cancer
(Int J Cancer)
Vol. 72
Issue 1
Pg. 95-101
(Jul 03 1997)
ISSN: 0020-7136 [Print] United States |
PMID | 9212229
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anticarcinogenic Agents
- Isothiocyanates
- 9,10-Dimethyl-1,2-benzanthracene
- phenethyl isothiocyanate
- Miconazole
- Anethole Trithione
- Acetylcysteine
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Topics |
- 9,10-Dimethyl-1,2-benzanthracene
- Acetylcysteine
(pharmacology)
- Anethole Trithione
(pharmacology)
- Animals
- Anticarcinogenic Agents
(pharmacology)
- Body Weight
(drug effects)
- Female
- Isothiocyanates
(pharmacology)
- Mammary Neoplasms, Experimental
(chemically induced, prevention & control)
- Miconazole
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Time Factors
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