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

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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.