Effects of hyperthermia on DNA interstrand crosslinking after treatment with BCNU in 9L rat brain tumor cells.
Effects of hyperthermia on DNA interstrand crosslinking after treatment with BCNU in 9L rat brain tumor cells.
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DOI：
10.2307/3576759
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发表时间：
1985-09
影响因子：
3.4
通讯作者：
P. Tofilon;V. D. Da Silva;P. Gutin;D. Deen
中科院分区：
文献类型：
--
作者：
P. Tofilon;V. D. Da Silva;P. Gutin;D. Deen
采用碱性洗脱技术研究了42 ℃高温对1，3-二（2-氯乙基）-1-亚硝基脲（BCNU）介导的9 L大鼠脑肿瘤细胞DNA链间交联形成的影响。当细胞在37 ℃下用60 μ M BCNU处理1小时并在42 ℃下在无药物培养基中孵育6小时时，交联增加了50%;当细胞在42 ℃下处理并在37 ℃下孵育时，与在37 ℃下处理并孵育的细胞的结果相比，交联增加了45%。当细胞在42 ℃下处理和孵育时，DNA交联增加了129%。发现细胞存活率的结果的相对顺序相同。这些结果表明，高温可以增加DNA链间交联的形成和随后的细胞死亡，通过两个独立的机制：在初始烷基化的量的增加，因为在较高的温度下的BCNU的水解速率增加，和热对DNA结构的影响，导致形成的交联的数量增加。
The effects of hyperthermia (42 degrees C) on 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-mediated DNA interstrand crosslink formation were investigated in 9L rat brain tumor cells using the technique of alkaline elution. When cells were treated with 60 microM BCNU for 1 hr at 37 degrees C and incubated for 6 hr in drug-free medium at 42 degrees C, there was a 50% increase in crosslinking; and when cells were treated at 42 degrees C and incubated at 37 degrees C, there was a 45% increase in crosslinking compared with the results for cells treated and incubated at 37 degrees C. When cells were treated and incubated at 42 degrees C, there was a 129% increase in DNA crosslinking. The same relative order of results was found for cell survival. These results suggest that hyperthermia can increase DNA interstrand crosslink formation and the consequent cell death through two independent mechanisms: an increase in the amount of initial alkylation because of the increased rate of hydrolysis of BCNU at higher temperatures, and the effect of heat on DNA structure that leads to an increase in the number of crosslinks formed.