Molecular characterization of mutations in the hprt gene of normal human skin keratinocytes treated with N‐ethyl‐N‐nitrosourea: Influence of O6‐alkylguanine alkyltransferase
Molecular characterization of mutations in the hprt gene of normal human skin keratinocytes treated with N‐ethyl‐N‐nitrosourea: Influence of O6‐alkylguanine alkyltransferase
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N-乙基-N-亚硝基脲处理的正常人皮肤角质形成细胞hprt基因突变的分子特征：O6-烷基鸟嘌呤烷基转移酶的影响
DOI：
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发表时间：
1997
影响因子：
2.8
通讯作者：
Steven M. D`Ambrosio
中科院分区：
文献类型：
--
作者：
H. Tong;Jeong;T. Brady;C. Weghorst;Steven M. D`Ambrosio
O6‐Alkylguanine‐DNA alkyltransferase (AGT) is responsible for repairing the O6‐alkylguanine lesion in DNA. There is wide variation in the levels of AGT between organ and cell types, which appears to correlate with cell and tissue type sensitivity to the mutagenic and carcinogenic effects of alkylating agents. In order to investigate the role of AGT in modulating the frequency and types of mutations induced in one type of normal human parenchymal cells, we examined the types and frequency of mutations in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene in 116 mutants derived from two N‐ethyl‐N‐nitrosourea (ENU)‐treated normal human skin keratinocyte cell lines. O6‐Benzylguanine (O6‐BZ; 5 μM × 2 hours) was used to specifically inhibit AGT activity before ENU treatment (0 to 5 mM × 1 hour). O6‐BZ increased both the cytotoxic and mutagenic effects of ENU by 1.8‐ and 3‐ to 5‐fold, respectively. In both treatment groups, most of the mutations were base substitutions (72%). The proportion of GC to AT transitions in the O6‐BZgroup (14/31) was twice that in the group treated with ENU alone, consistent with the loss of AGT activity in these cells. There was no strand specificity of GC to AT and AT to GC transitions in both groups. Base transversions accounted for 28% of total base substitutions. A lower than expected proportion of AT to TA transversions were observed in both cell lines, which decreased in the O6‐BZ pretreated group. A strand bias was observed for GC to TA and AT to TA transversions. Most of the G to A and G to T base substitutions had one or more purines flanking 3′ to the mutated deoxyguanosines. There were more deletion mutants with the deletion of exon 1, 4, 6, and 8 in the BZ group than in the control group. These data, characterizing the mutational spectra of ENU in normal human keratinocytes treated in vitro, indicate that GC to AT and AT to GC transition mutations predominate in these cells depleted or not depleted of AGT. Environ. Mol. Mutagen. 29:168–179, 1997. © 1997 Wiley‐Liss, Inc.
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影响因子：
4.7
作者：
Bernd Kaina;Gerhard Fritz;Sankar Mitra;T. Coquerelle
通讯作者：
Bernd Kaina;Gerhard Fritz;Sankar Mitra;T. Coquerelle
修复O6-甲基鸟嘌呤对正常人体组织的损伤。
DOI：
10.1007/978-1-4613-0637-5_31
发表时间：
1990
期刊：
Basic life sciences
影响因子：
--
作者：
D'Ambrosio,SM;Wani,G;Samuel,M;Gibson-D'Ambrosio,R;Wani,AA
通讯作者：
Wani,AA
缺乏 DNA 损伤介导的对致癌前 O6-甲基鸟嘌呤特异的人类甲基转移酶的诱导。
DOI：
10.1002/tcm.1770090502
发表时间：
1989
期刊：
Teratogenesis, carcinogenesis, and mutagenesis
影响因子：
--
作者：
Wani,G;Wani,AA;Gibson-D'Ambrosio,R;Samuel,M;Lowder,E;D'Ambrosio,SM
通讯作者：
D'Ambrosio,SM
N3-乙基脱氧胸苷在乙基化剂诱变和细胞毒性中的作用。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Grevatt,PC;Donahue,JM;Bhanot,OS
通讯作者：
Bhanot,OS
修复人体细胞中O4-烷基胸腺嘧啶损伤。
DOI：
10.1007/978-1-4613-0637-5_32
发表时间：
1990
期刊：
Basic life sciences
影响因子：
--
作者：
Wani,AA;Wani,G;D'Ambrosio,SM
通讯作者：
D'Ambrosio,SM