Nagasawa H, Fornace A J, Little J B
Department of Cancer Biology, Harvard University School of Public Health, Boston, MA 02115.
Mutat Res. 1988 Mar;198(1):153-60. doi: 10.1016/0027-5107(88)90050-4.
The relationship between cytotoxicity, sister-chromatid exchanges (SCE) and the repair of DNA crosslinks was studied in mouse 10T1/2 cells during confluent holding following either acute or protracted MMC treatment. No cytotoxic effects were observed with increasing doses of MMC until SCE frequencies 1.8 times background levels were induced. Protracted MMC treatments were less cytotoxic than acute MMC exposure at doses which yielded similar frequencies of SCE. The kinetics of recovery during confluent holding in acute MMC-treated cells were similar for cytotoxicity and the repair of DNA interstrand crosslinks. These results suggest that a type of non-lethal DNA damage which causes SCE may persist for long periods of time in MMC-treated cells. This non-lethal damage may accumulate during protracted MMC exposure while damage leading to cell killing is repaired.
在急性或长时间丝裂霉素C(MMC)处理后的汇合培养期,研究了小鼠10T1/2细胞中细胞毒性、姐妹染色单体交换(SCE)与DNA交联修复之间的关系。在诱导SCE频率达到背景水平的1.8倍之前,随着MMC剂量增加未观察到细胞毒性作用。在产生相似SCE频率的剂量下,长时间MMC处理的细胞毒性低于急性MMC暴露。急性MMC处理的细胞在汇合培养期恢复的动力学,对于细胞毒性和DNA链间交联的修复而言是相似的。这些结果表明,一种导致SCE的非致死性DNA损伤可能在MMC处理的细胞中长时间持续存在。这种非致死性损伤可能在长时间MMC暴露期间积累,而导致细胞死亡的损伤则被修复。