Assessment of in vivo chemotherapy-induced DNA damage in a p53-mutated rat tumor by micronuclei assay
Assessment of in vivo chemotherapy-induced DNA damage in a p53-mutated rat tumor by micronuclei assay
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DOI：
10.1196/annals.1299.139
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Bruyns, C
中科院分区：
文献类型：
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作者：
Driessens, G;Harsan, L;Bruyns, C
DNA损伤的产生是癌症治疗如化疗和放疗的基础。这样的治疗。诱导有丝分裂灾难，一种由异常有丝分裂引起的细胞死亡形式，并导致形成具有多个微核的间期细胞。在这项研究中，我们比较了细胞凋亡诱导和微核形成，以评估在体内细胞毒性药物引起的DNA损伤，在建立9 L大鼠胶质肉瘤肿瘤表达突变的p53基因。TUNEL分析的结果揭示了肿瘤部位的局部γ-照射在9 L肿瘤块内诱导细胞凋亡的效率。然而，在全身（ip）注射顺铂（1 mg/kg）后，很少或没有检测到细胞凋亡。有趣的是，微核试验表明，不仅γ射线照射，而且顺铂治疗导致出现微核双核细胞的增加。因此，细胞凋亡诱导和微核出现并非绝对相关。然而，微核试验，很少在实体瘤中进行，似乎更敏感的比细胞凋亡试验在评估与化疗相关的DNA损伤。
Production of DNA damage is the basis of cancer treatments such as chemo- and radiotherapy. Such treatments. induce mitotic catastrophe, a form of cell death resulting from abnormal mitosis and leading to the formation of interphase cells with multiple micronuclei. In this study, we compared apoptosis induction and micronuclei formation to assess the DNA damage provoked in vivo by cytotoxic agents in established 9L rat gliosarcoma tumors expressing a mutated p53 gene. Results from TUNEL assays revealed the efficiency of local gamma-irradiation at the tumor site to induce apoptosis within 9L tumor mass. However, little or no apoptosis was detected after systemic (ip) injection of cisplatin (1 mg/kg). Interestingly, the micronuclei assays showed that not only gamma-irradiation but also cisplatin treatment led to an increase in the emergence of binucleated cells with micronuclei. Apoptosis induction and micronuclei emergence are thus not absolutely correlated. However, micronuclei assays, rarely performed on solid tumors, appear more sensitive than apoptosis assays in evaluating DNA damage linked to chemotherapy.