Differences between the mutational consequences of replication of cis- and trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyguanosine adducts in M13mp7L2 constructs.
Differences between the mutational consequences of replication of cis- and trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyguanosine adducts in M13mp7L2 constructs.
复制标题
M13mp7L2 构建体中顺式和反式开放苯并[a]芘 7,8-二醇 9,10-环氧化物-脱氧鸟苷加合物复制的突变后果之间的差异。
DOI：
10.1021/tx0002684
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发表时间：
2001
影响因子：
4.1
通讯作者：
Jerina,DM
中科院分区：
文献类型：
--
作者：
Ponten,I;Kroth,H;Sayer,JM;Dipple,A;Jerina,DM
从7,8-二羟基-9,10-环氧-7,8,9,10-四氢苯并[a]芘的四个旋光异构体的C-10顺开得到的脱氧鸟苷的四个加合物atn2在划线位置被纳入5 ' -TTCGAATCCTTCCCCC[上下文III(G)]和5 ' -GGGGTTCCCGAGCGGC[上下文IV(G)]。在将修饰的寡核苷酸连接到单链M13mp7L2上并在sos诱导的大肠杆菌中复制载体后，研究了这两种序列背景下这些病变的致突变后果。碱基取代突变的总频率在14%到48%之间。背景IV(G)的突变频率普遍高于背景III(G)，主要是G→T碱基替换，然后是G→C碱基替换。在上下文IV(G)中，所有加合物中也发现了大量的一个鸟嘌呤的缺失或插入，其中加合物位于5个鸟嘌呤的3 '端。顺式打开的加合物诱导的碱基取代突变的总体频率明显高于相同序列中反式打开的dGuo加合物[Page et al. (1998) biochemistry, 37, 9127−9137]。虽然顺式和反式打开的加合物以G→T碱基取代为主，但顺式打开的dGuo加合物通常导致G→C的比例高于G→a[特别是在上下文III(G)中]，而反式打开的dGuo加合物则相反。目前的结果以及以前的数据表明，诱变性高度依赖于序列背景和加合物立体化学的组合。
The four adducts atN2of deoxyguanosine derived from cis-opening at C-10 of four optically active isomers of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene were incorporated into 5‘-TTCGAATCCTTCCCCC [context III(G)] and 5‘-GGGGTTCCCGAGCGGC [context IV(G)] at the underlined site. The mutagenic consequences of these lesions in each of the two sequence contexts were examined after ligation of the modified oligonucleotides into single-stranded M13mp7L2 and replication of the vector in SOS-inducedEscherichia coli.Total frequencies of base substitution mutations ranged between 14 and 48%. The mutation frequencies were generally higher in context IV(G) than in context III(G), and consisted mainly of G→T followed by G→C base substitutions. A substantial number of deletions or insertions of one guanine was also found for all adducts in context IV(G), where the adduct is located at the 3‘-end of a run of five guanines. The overall frequencies of base substitution mutations induced by cis-opened adducts were substantially higher than those observed with the trans-opened dGuo adducts in the same sequences [Page et al. (1998)Biochemistry37, 9127−9137]. Although G→T base substitutions predominated for both the cis- and trans-opened adducts, the cis-opened dGuo adducts generally resulted in a higher proportion of G→C [particularly in context III(G)] relative to G→A, whereas the opposite was true for the trans-opened dGuo adducts. The present results along with previous data indicate that mutagenicity is highly dependent on a combination of sequence context and adduct stereochemistry.