Chemopreventive efficacy of anethole trithione, N‐acetyl‐L‐cysteine, miconazole and phenethylisothiocyanate in the DMBA‐induced rat mammary cancer model

• Published in: International journal of cancer Vol. 72; no. 1; pp. 95 - 101
• Main Authors: Lubet, Ronald A., Steele, Vernon E., Eto, Isao, Juliana, M. Margaret, Kelloff, Gary J., Grubbs, Clinton J.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 03.07.1997; Wiley-Liss
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Acetylcysteine - pharmacology; Anethole Trithione - pharmacology; Animals; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Body Weight - drug effects; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Female; Isothiocyanates - pharmacology; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Miconazole - pharmacology; Rats; Rats, Sprague-Dawley; Time Factors; Tumors; Imidazole derivatives; Animal model; Chemoprophylaxis; Carcinoma; Rat; Rodentia; Acetylcysteine; Malignant tumor; Anticarcinogen; Prevention; Mammary gland diseases; Carcinogen; Vertebrata; Mammalia; Animal; Organic isothiocyanate; Mammary gland; Miconazole
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970703)72:1<95::AID-IJC14>3.0.CO;2-9

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. Int. J. Cancer 72:95–101, 1997. © 1997 Wiley‐Liss Inc.