Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2148859 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2008 | 9 Pages |
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:3â²,2â²-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.
Keywords
Trp-P-2DMNCDNBG6PG6PDHGlu-P-1XODMeIQxCuZn-SODPhIPTrp-P-12-aminoanthraceneo-AminoazotolueneGlu-P-2DAF2-aminodipyrido[1,2-a:3′,2′-d]imidazoleGSTGSHCyPMeAαCPCBN,N-dimethylnitrosamineN-hydroxylationXanthine oxidase1-chloro-2,4-dinitrobenzene2-amino-3-methyl-9H-pyrido[2,3-b]indole2-amino-3-methylimidazo[4,5-f]quinoline2-aminofluoreneAFB1O2−Aflatoxin B1Heterocyclic amineInternational Agency for Research on CancerIARC یا International Agency for Research on CancerBenzo[a]pyreneMutagenicityOatSuperoxide anion radicalSalmonella TyphimuriumCytosolCytochrome P450copper, zinc-superoxide dismutasepolychlorobiphenylreduced glutathioneglutathione S-transferaseglucose-6-phosphateglucose-6-phosphate dehydrogenase
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Hiroaki Nii, Masato Tsutsui, Jun Kondo, Yumiko Toyohira, Susumu Ueno, Nobuyuki Yanagihara,