Mutation Research, 283 (1992) 45-52 © 1992 Elsevier Science Publishers B.V. All rights reserved 0165-7992/92/$05.00

45

MUTLET 0699

Mutagenicity of nitro-polycyclic aromatic hydrocarbons with the nitro substituent situated at the longest molecular axis Shuyi Yu *, Diogenes Herreno-Saenz, Dwight W. Miller, Fred F. Kadlubar and Peter P. Fu National Center for Toxicological Research, Jefferson, AR 72079, USA (Received 5 November 1991) (Revision received 31 March 1992) (Accepted 22 April 1992)

Keywords: Nitro-polycyclic aromatic hydrocarbons; Nitro-PAHs

Nitro-polycyclic aromatic hydrocarbons (nitroPAl-Is) are environmental contaminants and are present in the food chain (Pitts et al., 1978; Rosenkranz and Mermelstein, 1983; Schuetzle, 1983; Paputa-Peck et al., 1983; Beland et al., 1985; Tokiwa and Ohnishi, 1986; Fu, 1990; Howard et al., 1991). Since many nitro-PAHs are metabolized to highly mutagenic and tumorigenic metabolites by mammalian and/or bacterial enzymes, there is concern regarding possible adverse human health effects from exposure to these compounds (E1-Bayoumy et al., 1982, 1989; Correspondence: Dr. Peter P. Fu, National Center for Toxicological Research, Jefferson, AR 72079, USA. * Visiting Scientist, Institute of Environmental Health and Engineering, Chinese Academy of Preventive Medicine, Beijing, People's Republic of China.

Abbrevmtions: Nitro-PAHs, nitro-polycyclic aromatic hydrocarbons; 2-nitro-BaP, 2-nitrobenzo[a]pyrene; other nitrobenzo[a]pyrenes are similarly abbreviated; 2-nitro-Hs-BaP, 2-nitro-4,5,7,8,9,10,11,12-octahydrobenzo[ a]pyrene; 2-nitroH6-chrysene, 2-nitro-7,8,9,10,11,12-hexahydrochrysene; 3nitro-H6-BA, 3-nitro-5,6,8,9,10,11-hexahydrobenz[ a ]anthracene; 3-nitro-DiBA, 3-nitrobenz[a,h]anthracene; 3-nitro-H 4DiBA, 3-nitro-5,6,12,13-tetrahydrobenz[ a,h ]anthracene; DMSO, dimethyl sulfoxide; HPLC, high-performance liquid chromatography.

Rosenkranz and Mermelstein, 1983; Beland et al., 1985; Tokiwa and Ohnishi, 1986; Fu, 1990; Wislocki et al., 1986; Imaida et al., 1991). Previous studies on the mutagenicity, metabolism and DNA binding of nitro-PAils indicate that both reduction of the nitro substitutent (nitroreduction) and ring-oxidation followed or preceded by nitroreduction are important metabolic activation pathways (Rosenkranz and Mermelstein, 1983; Fu et al., 1988a; Howard et al., 1983; E1-Bayoumy and Hecht, 1984; Chou et al., 1985, 1986; Delclos et al., 1988). We have been interested in structure-activity relationships as a means of utilizing the structural and electronic features of nitroPAils for the interpretation and/or prediction of their metabolism and their biological activities, including mutagenicity (Fu et al., 1988c; Fu, 1990; Jung et al., 1991). Recent studies by several groups have suggested that the first half-wave reduction potential (Klopman et al., 1984; Fu et al., 1988b; Fu, 1990; Jung et al., 1991), the molecular dimensions and degree of aromaticity (Vance and Levin, 1984; Fu et al., 1988c; Fu, 1990; Jung et al., 1991), the geometric location and the orientation of the nitro substituent (Vance and Levin, 1984; Fu et al., 1985, 1986, 1988a,b,c, 1989; Fu, 1990; Jung et al., 1991), and the number of electrons involved in the first step of nitroreduction (Eddy et al.,

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