Hatayama T, Goldberg I H
Biochim Biophys Acta. 1979 Jun 20;563(1):59-71. doi: 10.1016/0005-2787(79)90007-8.
To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug.
为阐明新制癌菌素对哺乳动物细胞的杀伤活性机制，对药物诱导的DNA损伤及其修复进行了研究。在极低剂量的新制癌菌素作用下，细胞存活率较高，此时DNA明显产生单链断裂以及“DNA复合物”分解，但这些损伤似乎几乎能完全修复。在较高剂量的新制癌菌素作用下，单链断裂能在很大程度上得到修复，而双链断裂似乎无法修复。不可修复的单链断裂数量约为双链断裂的两倍。这意味着除了构成双链断裂的单链断裂外，其他单链断裂均可修复。尽管在低剂量新制癌菌素作用下双链断裂可能会发生修复，但新制癌菌素处理的细胞集落形成能力与不可修复的DNA断裂之间的相关性表明，每个细胞产生少量关键的不可修复双链断裂可能是该药物具有细胞杀伤活性的原因。
