Mutation Research, 225 (1989) 181-187 181 Elsevier MTRL 0190 Mutagenicity of nitrofurantoin and furazolidone in Chinese hamster ovary cell strains Ning Gao*, Yi-Chang Ni**, Janice R. Thornton-Manning, Peter P. Fu and Robert H. Heflich National Center for ToxicologicalResearch, Jefferson, AR 72079 (U.S.A.) (Accepted 17 November 1988) Keywords: Nitrofurantoin; Furazolidone; Chinese hamster ovary cells Nitrofurantoin and furazolidone are 2-sub- stituted 5-nitrofurans that are used as human medicines, nitrofurantoin for treating urinary tract infections and furazolidone for gastrointestinal in- fections (Physicians Desk Reference, 1987). Fura- zolidone is also used in veterinary medicine and as a feed supplement for chickens and swine. In view of their potent mutagenicity in bacteria (reviewed in Klemencic and Wang, 1978) and their tumorige- nicity in laboratory animals (FDA, 1976, 1984; Maronpot, 1987), nitrofurantoin and furazolidone may also present a genotoxic risk to humans. * Permanent address: Drug Inspection Institute of Inner Mongolia, Huhhot (People's Republic of China). ** Permanent address: Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai (People's Republic of China). Correspondence: Dr. Robert H. Heflich, Division of Genetic Toxicology, National Center for Toxicological Research, Jef- ferson, AR 72079 (U.S.A.). Abbreviations: CHO, Chinese hamster ovary; $9, liver homogenate fraction; FBS, fetal bovine serum; DMSO, dimethyl sulfoxide; 6-TG, 6-thioguanine. The correspondence between the bacterial mutagenicity and animal tumorigenicity of nitro- furantoin and furazolidone may be fortuitous, since the mutagenic responses produced by nitro- furans in bacteria appear to be largely the result of bacterial metabolism (McCalla, 1983; Ni et al., 1987) and these pathways may not be relevant to the carcinogenic potential of these compounds. To further investigate their genotoxicity in mamma- lian systems, the mutagenicity of nitrofurantoin and furazolidone was evaluated using Chinese hamster ovary (CHO) cells and two CHO cell derivatives, AS52, which possesses the bacterial gpt gene as its mutational target (Tindall et al., 1984), and UV5, which is deficient in DNA exci- sion repair (Thompson et al., 1980, 1982, 1984). These alterations render AS52 cells hypersensitive to the mutagenicity of agents that produce large deletions in DNA (Stankowski and Tindall, 1988) and UV5 cells hypersensitive to agents that pro- duce bulky DNA adducts (Thompson, 1985; Thompson and Hoy, 1986). By using these three cell strains we sought to determine, (1) whether or not these ceils could detect any mutagenicity pro- duced by these known carcinogens, and (2) infor- mation concerning the nature of any mutagenic damage formed in these cells. 0165-7992/89/$ 03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)