DNA repair and malignant transformation: effect of X irradiation, 12-O-tetradecanoyl-phorbol-13-acetate, and protease inhibitors on transformation and sister-chromatid exchanges in mouse 10T 1/2 cells.
DNA repair and malignant transformation: effect of X irradiation, 12-O-tetradecanoyl-phorbol-13-acetate, and protease inhibitors on transformation and sister-chromatid exchanges in mouse 10T 1/2 cells.
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DNA 修复和恶性转化：X 射线照射、12-O-十四烷酰基-佛波醇-13-乙酸酯和蛋白酶抑制剂对小鼠 10T 1/2 细胞转化和姐妹染色单体交换的影响。
DOI：
10.2307/3575095
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发表时间：
1979
影响因子：
3.4
通讯作者：
A. Kennedy
中科院分区：
文献类型：
--
作者：
J. Little;H. Nagasawa;A. Kennedy
我们研究了密度抑制小鼠10 T 1/2细胞在从潜在致死性X射线损伤（PLD）中恢复过程中发生的存活率和染色体畸变、姐妹染色单体交换（SCE）和恶性转化频率的变化。在恢复的前4小时内，存活率、转化率和SCE平行增加，但畸变率减少。随着4至12小时的恢复间隔，没有进一步的变化，在生存或畸变，但是，转化和SCE显着下降。X射线单独或与肿瘤促进剂12-O-十四烷酰基-佛波醇-13-乙酸酯（TPA）组合诱导的转化通过暴露于蛋白酶抑制剂antipain而被抑制。在PLD恢复实验中，TPA被发现，以提高自发和直接X射线诱导（无恢复）SCE，但恢复诱导SCE没有影响。同时暴露于抗痛剂或亮抑酶肽抑制TPA和恢复诱导的SCE，但不直接X射线诱导的SCE。通过两个假设对这些结果进行了讨论：（1）X射线照射诱导的DNA损伤和修复过程可能有两种生物学上重要的类型，一种主要负责细胞杀伤，另一种主要导致突变和转化，（2）SCE反映的有丝分裂重组在转化方面是辐射损伤表达中的一个重要步骤，因为它允许在子细胞群中分离X射线诱导的隐性突变。«少
We have examined the changes which occur in survival and in the frequencies of chromosomal aberrations, sister-chromatid exchanges (SCE), and malignant transformation during recovery from potentially lethal x-ray damage (PLD) in density-inhibited mouse 10T 1/2 cells. During the first 4 h of recovery, there was a parallel increase in survival, transformation, and SCE but a decrease in aberrations. With recovery intervals of 4 to 12 h, there was no further change in survival or aberrations; however, both transformation and SCE declined markedly. Transformation induced by X rays alone or in combination with the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was suppressed by exposure to the protease inhibitor antipain. In PLD-recovery experiments, TPA was found to enhance both spontaneous and direct x-ray-induced (no recovery) SCE but to have no effect on recovery-induced SCE. Concomitant exposure to antipain or leupeptin suppressed the TPA and recovery-induced SCE but not the direct x-ray-induced SCE. These results are discussed in terms by two hypotheses: (1) that there may be two biologically important classes of DNA lesions and repair processes induced by X irradiation, one primarily responsible for cell killing and one which leads primarily to mutations and transformations and (2) that mitotic recombination reflected by SCE ismore » an important step in the expression of radiation damage in termsof transformation, as it allows segregation of x-ray-induced recessive mutations in daughter cell populations.« less