title: Copper, zinc-superoxide dismutase enhances the mutagenicity in Salmonella typhimurium induced by 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole.
abstract: The mutagenicities of various carcinogens induced by liver microsomes are increased in the presence of liver cytosol in rodents. It still remains, however, to be clarified which factor or factors in the cytosol enhance(s) the microsome-mediated mutagenicities. In the present study, we sought to identify the enhancing factor in liver cytosol prepared from rats using the microsome-mediated Salmonella mutagenicity induced by 2-amino-6-methyldipyrido [1,2-a:3',2'-d] imidazole (Glu-P-1). By a series of chromatographic steps, we purified a 16-kDa protein on SDS-PAGE from the cytosol of rat livers. Partial amino acid sequences of this protein revealed that the 16-kDa protein was copper, zinc-superoxide dismutase (CuZn-SOD). The purified CuZn-SOD enhanced the microsome-mediated mutagenicities of several heterocyclic amines and aromatic amines. Furthermore, bovine and human CuZn-SOD also enhanced the microsome-mediated mutagenicity of Glu-P-1. The CuZn-SOD caused an increase in the mutagenicity of N-hydroxylated Glu-P-1 formed from Glu-P-1 by the microsomes, although CuZn-SOD did not affect either the formation or the stability of the N-hydroxylated derivative. These findings suggest that the enhancing cytosol factor for the mutagenicity of Glu-P-1 is CuZn-SOD, which stimulates the mutagenicity of N-hydroxylated Glu-P-1 without changing its metabolism.
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Yahatanishi-ku, Kitakyushu 807-8555, Japan. niih@med.uoeh-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nii
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Jun
authors.initials: J
authors.lastname: Kondo
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000235:genetics*; D013482:Superoxide Dismutase / Q000494:pharmacology*
chemical_list: D007093:Imidazoles; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D013482:Superoxide Dismutase