Effects of Multiple Putative Anticarcinogens on the Carcinogenicity of trans-5-Amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole

• Published in: JNCI : Journal of the National Cancer Institute 1984-07, Vol.73 (1), p.161-168
• Main Authors: Dunsford, Harold A., Dolan, Patrick M., Seed, John L., Bueding, Ernest
• Format: Article
• Language: English
• Subjects: 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole - antagonists & inhibitors; 5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole - toxicity; Adenocarcinoma - chemically induced; Animals; Antineoplastic Agents; Antioxidants - therapeutic use; Carcinogens; Carcinoma, Squamous Cell - chemically induced; Female; Leukemia, Experimental - chemically induced; Lung Neoplasms - chemically induced; Lymphoma - chemically induced; Mice; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - prevention & control; Nitrofurans - toxicity; Sarcoma, Experimental - chemically induced
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/73.1.161

In an attempt to dissociate the chemotherapeutic from the carcinogenic properties of the antischistosomal and antitrypanosomal nitrovinylfuran trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole [(SQ18506) CAS: 28754-68-9; (E)-5-amino-3-(2-(5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole], potential inhibitors of carcinogenesis were administered to female outbred CD-1 mice before and during exposure to SQ18506. The compounds tested were ascorbic acid, etretinate, butylated hydroxyanisole (BHA), cysteamine hydrochloride, cysteine hydrochloride, dimercaprol, disulfiram, 1,4-dithiothreitol, reduced glutathione, and spermidine phosphate. The primary types of tumors observed were squamous cell carcinomas of the stomach and thymic and nonthymic lymphomas. BHA reduced the incidence of malignant tumors to control levels, whereas cysteine hydrochloride, spermidine phosphate, and disulfiram reduced the incidence of chemically induced tumors by 42, 34, and 32%, respectively. Although cysteamine hydrochloride and disulfiram had no or only a modest effect on the overall incidence of tumors, the data suggested possible tissue-specific anticarcinogenic properties for these agents. Of the 8 antioxidants tested, only 1 had marked anticarcinogenic properties against SQ18506. These data indicate that antioxidant properties alone cannot account for the anticarcinogenic activity of the compounds tested. Coadministration of the anticarcinogen BHA with SQ18506 also blocked the chemotherapeutic effects of this agent on female CD-1 mice infected with Schistosoma mansoni.