Anensen H, Provan F, Lian A T, Reinertsen S H, Ueno Y, Matsuda A, Seeberg E, Bjelland S
School of Science and Technology, Stavanger University College, Ullandhaug, P.O. Box 2557, N-4091 Stavanger, Norway.
Mutat Res. 2001 May 9;476(1-2):99-107. doi: 10.1016/s0027-5107(01)00086-0.
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.
5-甲酰基尿嘧啶(5-foU)是胸腺嘧啶的主要氧化产物,其在DNA中由电离辐射产生的产量与8-氧代鸟嘌呤相当。虽然8-氧代鸟嘌呤的诱变作用已得到充分了解,但迄今为止,对5-foU生物学意义的研究还很有限。在此,我们证明,向大肠杆菌生长培养基中添加5-甲酰基-2'-脱氧尿苷(5-fodUrd)会在lacZ基因第461位以不同频率诱导几种碱基替换,顺序如下:A.T→G.C>G.C→A.T>G.C→T.A>>A.T→T.A>A.T→C.G。未观察到G.C→C.G颠换的诱导。据推测,5-fodUrd在细胞生长过程中会掺入DNA,在复制过程中与鸟嘌呤、胞嘧啶和胸腺嘧啶形成错配。因此,在5-fodUrd存在下的细胞生长似乎可能是阐明DNA中5-foU残基细胞效应的良好模型。