Marchand M, Caspar P, Boon T
Eur J Cancer Clin Oncol. 1983 Nov;19(11):1529-37. doi: 10.1016/0277-5379(83)90082-2.
A previous report from this laboratory demonstrated that treatment of mouse mastocytoma P815 with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) produces tumor cell variants that are unable to form tumors in syngeneic animals. We examined whether repeated mutagen treatment could increase the frequency of tum- variants above that obtained after a single treatment. This was found to occur with frequencies increasing from a few percent after 1 treatment to more than 90% after 8 treatments. Moreover, uncloned survivor populations obtained after 8 or more MNNG cycles that contained such a high proportion of tum- variants had a markedly decreased tumorigenicity for syngeneic mice. As reported for tum- variants obtained after 1 mutagen treatment, several tum- variants obtained after repeated treatments carried new variant-specific antigens that elicited a specific cytolytic T cell response. Some of these tum- antigens were found to consist of multiple determinants that could be lost independently. We observed that the resistance of the mutagenized populations to MNNG increased gradually with the number of mutagen treatments. In addition, some tum- variants obtained after 8 mutagen treatments showed a reduced sensitivity to mitomycin C.
本实验室之前的一份报告表明，用诱变剂N-甲基-N'-硝基-N-亚硝基胍（MNNG）处理小鼠肥大细胞瘤P815会产生肿瘤细胞变体，这些变体在同基因动物中无法形成肿瘤。我们研究了重复诱变处理是否能使肿瘤变体的频率高于单次处理后的频率。结果发现确实如此，频率从单次处理后的百分之几增加到8次处理后的90%以上。此外，在经过8次或更多次MNNG处理后获得的未克隆存活群体中，含有如此高比例肿瘤变体的群体对同基因小鼠的致瘤性明显降低。正如单次诱变处理后获得的肿瘤变体的报道一样，重复处理后获得的几个肿瘤变体携带了新的变体特异性抗原，可引发特异性细胞溶解T细胞反应。其中一些肿瘤抗原被发现由多个可独立丢失的决定簇组成。我们观察到，诱变群体对MNNG的抗性随着诱变处理次数的增加而逐渐增强。此外，8次诱变处理后获得的一些肿瘤变体对丝裂霉素C的敏感性降低。
