کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5860327 1133178 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantification and repair of psoralen-induced interstrand crosslinks in human cells
ترجمه فارسی عنوان
اندازه گیری و اصلاح پیوندهای میانرشتی ناشی از پسورال در سلول های انسانی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی

Bi-functional alkylating agents that cause crosslinks are commonly used in chemotherapy. However, there is no conclusive knowledge for human cells regarding the number of induced interstrand crosslinks (ICLs) and the unhooking rate when the lesion is removed from one of the DNA strand. Using a newly developed method, we quantified the number of induced ICLs for the five furocoumarins; psoralen, 5-methoxypsoralen, 8-methoxypsoralen, tri-methoxypsoralen and angelicin. In quantitative terms, the results were in agreement with the values found by others. In kinetic studies using mammalian cells, we found that half of the psoralen-induced ICLs were unhooked within 2.5 h. The rate in normal human diploid fibroblasts was found to be 20,000 ICLs/h/cell. In comparison to survival, 2500 ICLs per cell led to 50% toxicity, indicating that the unhooking of the ICLs is not the crucial step for ICL tolerance. Surprisingly, only 3500 ICLs per cell corresponded to a significant delay in the replication fork elongation. The results indicate involvements of additional pathway(s) for the delay since the effect on replication elongation could be monitored when only 10% of the replication forks encounter an ICL.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 226, Issue 3, 2 May 2014, Pages 343-350
نویسندگان
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