摘要：To elucidate the cause of the difference in genotoxic activity between carcinogenic 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and noncarcinogenic 2-methoxy-4-aminoazobenzene (2-MeO-AAB), we analyzed DNA adducts in the livers of rats exposed to either of these chemicals and studied the resulting biologic potential with the aid of in vitro modified M13 phage DNA. 32P-Postalbeling analysis revealed that the carcinogen 3-MeO-AAB produced 20-fold higher amounts of adducts than did 2-MeO-AAB. Five adducts were formed in the 3-MeO-AAB case whereas only one adduct was apparent in 2-MeO-AAB-treated rat. Studies of in vitro DNA replication using N-hydroxy (N-OH)-aminoazo dye-modified M13 phage DNA as a template demonstrated inhibition by 3-MeO-AAB adducts to be substantially greater than in the 2-MeO-AAB-adducts. The specificity of mutagenesis induced in M13mp9 phage DNA by these chemicals also was analyzed after transfection into SOS-induced Escherichia coli JM103, mutation frequencies being higher with N-OH-3-MeO-AAB- than N-OH-2-MeO-AAB-modified DNA. The mutation spectra differed in each case. Our data suggest that the difference in hepatocarcinogenic activity between the two chemicals depends not only on qualitative and quantitative variation in adduct formation but also on conformation changes in modified DNA. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (863K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 191 192 193 194
Loading...
