Numata M, Hata H, Tohda H, Yasui A, Oikawa A
Department of Pharmacology, Tohoku University, Sendai, Japan.
Tohoku J Exp Med. 1992 Oct;168(2):123-8. doi: 10.1620/tjem.168.123.
1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutants (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chlorethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages.
1-[(4-氨基-2-甲基-5-嘧啶基)甲基]-3-(2-氯乙基)-3-亚硝基脲盐酸盐（ACNU）会导致DNA链发生氯乙基化，随后通过乙烯桥进行交联。我们最近从诱变的中国仓鼠卵巢细胞中分离出两个对ACNU敏感的突变体，并发现它们是新的药物敏感隐性突变体（Hata等人，1991年）。这些细胞的O6-甲基鸟嘌呤DNA甲基转移酶（MT）活性与亲代细胞系一样无法检测到，这表明突变细胞系对ACNU的敏感性并非由于该酶的细胞水平降低所致。通过与7个已建立的对紫外线敏感的CHO细胞系进行互补分析，其中一个突变体UVS1结果显示能够互补它们对紫外线的敏感性，因此，在所有已报道的CHO细胞系中形成了一个新的互补组。另一个突变体CNU1仅对氯乙基化剂（ACNU、CCNU）表现出超敏感性，并且由紫外线诱导的非计划DNA合成（UDS）略有降低。因此，提示该突变体在DNA修复系统的一个特定步骤中存在缺陷，这对于处理由ACNU产生的DNA损伤很重要。在7个已建立的对紫外线敏感的CHO突变体互补组中，只有第1组和第4组的细胞系比UVS1和CNU1对ACNU更敏感，这表明切除修复途径的一些步骤以及特定的修复系统在修复ACNU诱导的DNA损伤中起重要作用。
