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氧化损伤核苷酸5-甲酰基-dUTP和5-羟基-dCTP在大肠杆菌中诱导的突变。

The mutations induced by oxidatively damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP,in Escherichia coli.

作者信息

Fujikawa K, Kamiya H, Kasai H

机构信息

Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

出版信息

Nucleic Acids Res. 1998 Oct 15;26(20):4582-7. doi: 10.1093/nar/26.20.4582.

Abstract

The mutational properties of 5-formyl-2'-deoxyuridine 5'-triphosphate (5-CHO-dUTP) and 5-hydroxy-2'-deoxycytidine 5'-triphosphate (5-OH-dCTP), the major oxidatively damaged pyrimidine nucleotides derived from dTTP and dCTP, respectively, were analyzed by an in vivo assay. 5-CHO-dUTP and 5-OH-dCTP were directly incorporated into Escherichia coli , and their mutagenicities were evaluated by the chromosomal lacI forward mutation assay. The mutation frequencies increased, depending on the dose of these damaged nucleotides, indicating that these nucleotides were incorporated into E.coli and acted as mutagens in vivo . The mutagenicities of 5-CHO-dUTP and 5-OH-dCTP were comparable to that of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate, a major form of dGTP oxidative damage. 5-CHO-dUTP induced G.C to A.T, A.T to G.C and G.C to T.A mutations, and 5-OH-dCTP elicited G.C to A.T, A.T to C.G and G.C to T.A mutations.

摘要

通过体内试验分析了分别由脱氧胸苷三磷酸(dTTP)和脱氧胞苷三磷酸(dCTP)衍生而来的主要氧化性损伤嘧啶核苷酸5-甲酰基-2'-脱氧尿苷三磷酸(5-CHO-dUTP)和5-羟基-2'-脱氧胞苷三磷酸(5-OH-dCTP)的突变特性。将5-CHO-dUTP和5-OH-dCTP直接导入大肠杆菌,并通过染色体乳糖操纵子(lacI)正向突变试验评估它们的诱变性。突变频率随这些损伤核苷酸剂量的增加而升高,表明这些核苷酸被导入大肠杆菌并在体内起到诱变剂的作用。5-CHO-dUTP和5-OH-dCTP的诱变性与8-羟基-2'-脱氧鸟苷三磷酸(dGTP氧化性损伤的主要形式)相当。5-CHO-dUTP诱导G.C到A.T、A.T到G.C以及G.C到T.A的突变,而5-OH-dCTP引发G.C到A.T、A.T到C.G以及G.C到T.A的突变。

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