Nakano S, Koga T, Ichinose I, Nakayama M, Iwakiri R, Niho Y, Takaki R
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Mutat Res. 1989 Jan;217(1):45-51. doi: 10.1016/0921-8777(89)90035-9.
To determine the role of repair of potentially lethal damage (PLD) in the initiation process of neoplastic transformation, Balb/c 3T3 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were temporarily exposed to conditioned medium obtained from density-inhibited Chinese hamster cell cultures, as a post-treatment for the induction of PLD repair. With or without this exposure, cell survival and transformation frequencies were simultaneously determined by colony-formation and focus-formation assays, respectively. Temporary exposure to conditioned medium resulted in a 20-30% increase in cell survival compared with no exposure. Post-treatment with conditioned medium resulted in a 60-65% reduction in transformation frequencies. At the molecular level, the repair of MNNG-induced single-strand breaks of DNA occurred much more rapidly in conditioned medium. These data suggest that PLD repair reduces the in vitro neoplastic transformation through excision repair operative during the cessation of DNA replication. Thus, PLD repair appears to be preventive against neoplastic fixation in initiation of neoplastic development.
为了确定潜在致死性损伤（PLD）修复在肿瘤转化起始过程中的作用，用N-甲基-N'-硝基-N-亚硝基胍（MNNG）处理的Balb/c 3T3细胞被暂时暴露于从密度抑制的中国仓鼠细胞培养物中获得的条件培养基中，作为诱导PLD修复的后处理。无论有无这种暴露，分别通过集落形成和焦点形成试验同时测定细胞存活率和转化频率。与未暴露相比，暂时暴露于条件培养基导致细胞存活率提高20 - 30%。用条件培养基进行后处理导致转化频率降低60 - 65%。在分子水平上，MNNG诱导的DNA单链断裂在条件培养基中修复得更快。这些数据表明，PLD修复通过在DNA复制停止期间起作用的切除修复减少了体外肿瘤转化。因此，PLD修复似乎在肿瘤发生发展的起始阶段对肿瘤固定具有预防作用。
