| Abstrakt: |
The mutational specificity of -methylnitrosourea (MNU), nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), sodium azide (NaN) 4-nitroquinoline oxide (4NQO), benzo (BP), nitrofurantoin (NT), aflatoxin B (AFB adriamycin (ADM) and UVA-activated angelicin in Salmonella typhimurium strain TAIOO has been examined using allele-specific oligonudeotide hybridization and DNA sequence analyses. These ten mutagens produced five unique dasses of reversion spectra, distinct from spontaneous, or the previously characterized 5-azacytldine, ultraviolet light WV), 8-methoxypsoralen plus UVA (PUVA) and 60 mutation spectra. For example, 90% of MNU and MNNG induced mutations in strain TAIOO revertants were G:C-A:T transitions with the majority (82%) occurring in the first position of the CCC codon. In contrast, NaN preferentially induced G:C- transitions at the second codon position (78%). Although MMS, NQO, BP, NF, ADM and AFB induced primarily G:C-T:A transversions (73–86%), these mutagens fall into two dasses based on site preference: NF and AFB yielded almost exclusively position two transversion.s (69-78%) whereas ADM, NQO, BP and MMS exhibited a two-fold preference for site 2 over site 1 (on average 52% versus 22%). Angelicin photomutagenesis resulted in the recovery of G:C-A:T and G:C-T:A mutations at both codon positions in roughly equal proportions (˜20-25% each). Approximately 1% of the mutagen-induced revertants occurred via extragenic tRNA suppressor mutations, while 1% were multiple (usually tandem double) base substitutions. Ultraviolet mutagenesis experiments demonstrated that tandem base substitutions are promoted by pKM1O1-encoded mucAB gene products. A comparison of the mutagenic specificity derived for several carcinogens in with the responses of several eukaryotic gene targets (e.g. ) revealed a high concordance between these targets. Thus, the locus provides a rapid, simple system for determining base substitution specificity and for studying mechanisms of mutagenesis. [ABSTRACT FROM PUBLISHER] |
