Mutations induced by 5-formyl-2 '-deoxyuridine in Escherichia coli includebase substitutions that can arise from mispairs of 5-formyluracil with guanine, cytosine and thymine

5-Formyluracil (5-foU) is a major oxidation product of thymine formed in yi elds comparable to that of 8-oxoguanine in DNA by ionizing radiation. Where as the mutagenic effects of 8-oxoguanine are well understood, the investiga tion of the biological implications of 5-foU has so far been limited. Here we demonstrate that 5-formyl-2 ' -deoxyuridine (5-fodUrd) supplied to the g rowth medium of Escherichia coli induces several base substitutions at diff erent frequencies at position 461 in the lacZ gene in the following order: A . T --> G . C > G . C --> A . T > G . C --> T . A much greater than A . T --> T . A > A . T --> C . G. No induction of G C -, C G transversions was observed. It is inferred that 5-fodUrd will be incorporated into the DNA du ring cell growth, forming mispairs with guanine, cytosine and thymine durin g replication. It, thus, appears that cell growth in the presence of 5-fodU rd may represent a good model for elucidating the cellular effects of 5-foU residues in DNA. (C) 2001 Elsevier Science B.V. All rights reserved.