Mutations induced by 5-formyl-2'-deoxyuridine in Escherichia coli include base 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 yields comparable to that of 8-oxoguanine in DNA by ionizing radiation. Whereas the mutagenic effects of 8-oxoguanine are well understood, the investigation 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 growth medium of Escherichia coli induces several base substitutions at different frequencies at position 461 in the lacZ gene in the following order: A.T-->G.C>G.C-->A.T>G.C-->T.A>>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 during cell growth, forming mispairs with guanine, cytosine and thymine during replication. It, thus, appears that cell growth in the presence of 5-fodUrd may represent a good model for elucidating the cellular effects of 5-foU residues in DNA.
Anensen
H
H
School of Science and Technology, Stavanger University College, Ullandhaug, P.O. Box 2557, N-4091 Stavanger, Norway.
Provan
F
F
Lian
A T
AT
Reinertsen
S H
SH
Ueno
Y
Y
Matsuda
A
A
Seeberg
E
E
Bjelland
S
S
D020137:Base Pair Mismatch; D001483:Base Sequence; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D005798:Genes, Bacterial / Q000187:drug effects; D007763:Lac Operon / Q000187:drug effects; D008956:Models, Chemical; D016296:Mutagenesis; D009154:Mutation
D004269:DNA, Bacterial; C061519:5-formyl-2'-deoxyuridine; D003857:Deoxyuridine