Quantitative analysis of DNA interstrand cross-links and monoadducts formed in human cells induced by psoralens and UVA irradiation.
Quantitative analysis of DNA interstrand cross-links and monoadducts formed in human cells induced by psoralens and UVA irradiation.
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DOI：
10.1021/ac801520m
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发表时间：
2008-11-15
影响因子：
7.4
通讯作者：
Wang, Yinsheng
中科院分区：
文献类型：
--
作者：
Lai, Congfang;Cao, Huachuan;Hearst, John E.;Corash, Laurence;Luo, Hai;Wang, Yinsheng
当暴露于UVA光时，蛹虫草可以诱导DNA链间交联（ICL），其可以阻断DNA复制和转录。在牛皮癣衍生物中，8-甲氧基牛皮癣（8-MOP）通常用于牛皮癣治疗，而amotosalen S59用于抑制血液成分中的细菌和病毒病原体。除了ICL的形成外，当暴露于UVA光时，蛹虫草也容易与DNA中的胸苷残基形成各种单加合物（MA），这些单加合物的生物学意义尚不清楚。在这里，我们报告了一种方法，其中包括消化与一个单一的酶（核酸酶P1）和LC-MS/MS，用于同时定量ICL和MA诱导的人细胞暴露于8-MOP或S59和UVA光。结果表明，当UVA剂量从0.5 J/cm ~ 2增加到10.0 J/cm ~ 2时，S59诱导的ICL产量从3.9个/103个核苷酸增加到12.8个/103个核苷酸，是8-MOP诱导ICL产量的100倍。此外，3个和5个产物分别被鉴定为8-MOP-和S59-MAs，并且MAs的产率显著低于ICL。当UVA剂量从0.5增加到10.0 J/cm 2时，三种8-MOP-MA的产率为7.6-2.2、1.9-9.9和7.2-51/106核苷酸，五种S59-MA的产率为215-19、106-39、25-21、32-146和22-26/106核苷酸。虽然在相同的暴露条件下，8-MOP和S59诱导的MAs产量低于相应的ICL，但相当数量的MAs的形成可能解释了一些由peptides诱导的突变。
Upon exposure to UVA light, psoralens can induce DNA interstrand cross-links (ICLs), which can block DNA replication and transcription. Among the psoralen derivatives, 8-methoxypsoralen (8-MOP) is conventionally applied for psoriasis therapy, and amotosalen S59 is used to inactivate bacterial and viral pathogens in blood components. In addition to the ICL formation, psoralens also readily form various monoadducts (MAs) with thymidine residues in DNA when exposed to UVA light, and the biological implications for these monoadducts remain unclear. Here, we reported a method, which encompassed digestion with a single enzyme (nuclease P1) and LC-MS/MS, for the simultaneous quantification of ICL and MAs induced in human cells exposed with 8-MOP or S59 and UVA light. Our results showed that the yield of ICL induced by S59, which increased from 3.9 to 12.8 lesions per 103 nucleotides as the dose of UVA light increased from 0.5 to 10.0 J/cm2, was about 100 fold more than that induced by 8-MOP. In addition, three and five products were identified as 8-MOP- and S59-MAs, respectively, and the yields of MAs were significantly lower than that for ICL. The yields of the three 8-MOP-MAs were 7.6-2.2, 1.9-9.9 and 7.2-51 per 106 nucleotides and those of the five S59-MAs were 215-19, 106-39, 25-21, 32-146, and 22-26 per 106 nucleotides as the dose of UVA light increased from 0.5 to 10.0 J/cm2. Although the yields of MAs induced by 8-MOP and S59 were lower than those of the respective ICLs under the same exposure conditions, the formation of appreciable amounts of MAs might account for some of the mutations induced by psoralens.
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影响因子：
3.3
作者：
OLACK, G;GATTOLIN, P;GASPARRO, FP
通讯作者：
GASPARRO, FP
影响因子：
3.9
作者：
VIGNY, P;GABORIAU, F;CADET, J
通讯作者：
CADET, J
影响因子：
7.4
作者：
Wang, YS;Wang, YS
通讯作者：
Wang, YS
DOI：
10.1016/1044-0305(92)85019-g
发表时间：
1992-01-01
影响因子：
3.2
作者：
MCLUCKEY, SA;VANBERKEL, GJ;GLISH, GL
通讯作者：
GLISH, GL
影响因子：
4.7
作者：
BREDBERG, A;NACHMANSSON, N
通讯作者：
NACHMANSSON, N