尼莫司汀和雷莫司汀诱导大鼠胶质瘤细胞中的DNA不稳定性

Mineura K, Fushimi S, Itoh Y, Kowada M

Neurosurgical Service, Akita University Hospital, Japan.

J Neurol Neurosurg Psychiatry. 1988 Nov;51(11):1391-4. doi: 10.1136/jnnp.51.11.1391.

The DNA labile sites induced by two nitrosoureas, nimustine (ACNU) and ramustine (MCNU) synthesised in Japan, have been examined in highly reiterated DNA sequences of rat glioma cells. Reiterated fragments of 167 and 203 base pairs (bp), obtained after Hind III and Hae III restriction endonuclease digestion of rat glioma cells DNA, were used as target DNA sequences to determine the labile sites. In vitro reaction with ACNU and MCNU resulted in scission products corresponding to the locations of guanine. Subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at guanine positions, thus forming alkali-labile sites.

对日本合成的两种亚硝基脲类药物，尼莫司汀（ACNU）和雷莫司汀（MCNU）诱导的DNA不稳定位点，在大鼠胶质瘤细胞的高度重复DNA序列中进行了检测。经Hind III和Hae III限制性内切酶消化大鼠胶质瘤细胞DNA后获得的167和203碱基对（bp）的重复片段，用作确定不稳定位点的靶DNA序列。与ACNU和MCNU的体外反应产生了与鸟嘌呤位置相对应的断裂产物。随后的哌啶水解在鸟嘌呤位置导致磷酸二酯键更频繁地断裂，从而形成碱不稳定位点。