Mutation spectrum induced by dihydropyrazines in Escherichia coli

Abstract

Dihydropyrazine (DHP), which induces mutagenesis in E. coli, was investigated. From analyzing mutations in the chromosomal rpoB gene, the mutation spectrum in uvrB strain revealed the different behavior on exposure to two DHP derivatives 3-hydro-2,2,5,6-tetramethylpyrazine (HTMP), and 2,3-dihydro-5,6-dimethylpyrazine (DHDMP). A higher level of DHP-induced mutation was observed, with base substitutions at G : C pairs predominant. HTMP and DHDMP increased the frequency of G : C to T : A transversions. HTMP increased the frequency of G : C to A : T transitions, than did DHDMP. These findings suggest that DHPs prefer to attack the G:C pair and that different DHP derivatives may prefer distinct mutagenic base pairs; and further, that nucleotide excision repair may be involved in the repair of DHP-induced mutations. © 2006 Pharmaceutical Society of Japan.