Misincorporation of nucleotides opposite five-membered exocyclic ring guanine derivatives by escherichia coli polymerases in vitro and in vivo: 1,N2-ethenoguanine, 5,6,7,9-tetrahydro-9-oxoimidazo[1, 2-a]purine, and 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1, 2-a]purine.
1998
A variety of exocyclic modified bases have been shown to be formed in DNA from various procarcinogens (e.g., acrolein, malonaldehyde, vinyl chloride, urethan) and are also found in untreated animals and humans, presumably arising as a result of lipid peroxidation. 1,N2-Ethenoguanine (1,N2-e-Gua), a product known to be formed from several 2-carbon electrophiles, was placed in a known site (6256) in bacteriophage M13MB19 and mutations were analyzed in Escherichia coli, with 2.05% G→A, 0.74% G→T, and 0.09% G→C changes found in uvrA- bacteria. 5,6,7,9-Tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine (HO-ethanoGua), formally the hydrated derivative of 1,N2-e-Gua, is a stable DNA product also derived from vinyl halides. When this base was placed in the same context, the mutation rate was 0.007−0.19% for G→A, C, or T changes. The saturated etheno ring derivative of 1,N2-e-Gua, 5,6,7,9-tetrahydro-9-oxoimidazo[1,2-a]purine (ethanoGua) produced G→A and G→T mutations (0.71% each). All mutants were SOS-dependent and we...
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