Sequence analysis of X ray-induced and anticancer drug-induced mutations in cultured mammalian cells and peripheral blood lymphocytes

抗癌药物和环境致癌物有时会导致DNA碱基序列发生特殊类型的变化。这种类型的变化有助于估计接触这些化学品的人患癌症的风险，因为如果发现这种变化，可以归因于接触这些化学品的结果。用培养的CHO细胞研究新卡西诺抑素(NCS)诱导的突变，以确定是否存在这种特殊的变化。我们在NCS诱导的突变中发现了多种类型的突变(缺失、小缺失、移码和碱基改变)。这些类型的混合的比率与自发产生的突变的比率非常相似，这表明潜在的机制在一定程度上可能在这两种突变中共享。另一方面，在NCS处理的细胞中发现了碱基改变类型的突变的特征性变化。部分改变的碱基位于有AGC或ACT序列的突变部位，这在自发产生的突变中是没有的。众所周知，使用寡核苷酸时，NCS通过嵌入与DNA结合，从而使这些特定序列成为靶点。当研究人员想要确定继发性肿瘤的癌基因或抑癌基因突变是否是由抗癌药物NCS引起的时，这些发现将是有帮助的。NCS诱导的淋巴细胞突变目前正在进行中。

Anticancer drugs and environmental carcinogens sometimes cause a particular type of change in DNA base sequence. This type of change is useful to estimate the risk of cancer incidence of those who are exposed to these chemicals, as the change, if found, can be attributed to results of the exposure to these chemicals. The neocarzinostatin (NCS)-induced mutations were studied using cultured CHO cells, to determine if there is such a particular change. We found a variety of class of mutations (deletions, small deletions, frameshifts and base changes) in NCS-induced mutations. The rate of these classes of multations were quite similar to that of mutations arising spontaneously, suggesting that underlying mechanism may share to some extent in both mutations. On the other hand, a characteristic change was found in base change type of mutations in NCS-treated cells. The some of changed bases were at mutation site where there is AGC or ACT sequence, which was not found in mutations arising spontaneously. It is well known using oligonucleotide that NCS binds to DNA by intercalation so that these specific sequences are targeted. These findings would be helpful, when researchers want to identify whether or not mutations in oncogene or tumor suppressor gene in seocndary tumor are caused by NCS,an anticancer durg used for cancer treatment. The NCS-induced mutations in lymphocytes are now being underway.