Mitani H, Yagi T, Leiler C Y, Takebe H
Department of Experimental Radiology and Molecular Oncology, Faculty of Medicine, Kyoto University, Japan.
Carcinogenesis. 1989 Oct;10(10):1879-82. doi: 10.1093/carcin/10.10.1879.
Mouse Ha821 cells, Harvey murine sarcoma virus-transformed NIH3T3 cells, have extremely low O6-alkylguanine--DNA alkyltransferase (O6AGTase) activity and are hypersensitive to an anti-tumor chloroethylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The treatment of Ha821 cells with a DNA demethylating agent, 5-azacytidine, resulted in an increase in the frequency of ACNU-resistant cell clones. All randomly isolated ACNU-resistant cell clones were found to have O6AGTase activity comparable to the level of the parental NIH3T3 cells. These results suggest that reversible loss of O6AGTase activity in Ha821 cells is caused at least in part by inactivation of the O6AGTase gene due to methylation of cytosine in the gene.
小鼠Ha821细胞，即哈维鼠肉瘤病毒转化的NIH3T3细胞，具有极低的O6-烷基鸟嘌呤-DNA烷基转移酶（O6AGTase）活性，并且对一种抗肿瘤氯乙化剂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）高度敏感。用DNA去甲基化剂5-氮杂胞苷处理Ha821细胞，导致ACNU抗性细胞克隆的频率增加。所有随机分离的ACNU抗性细胞克隆都被发现具有与亲代NIH3T3细胞水平相当的O6AGTase活性。这些结果表明，Ha821细胞中O6AGTase活性的可逆丧失至少部分是由于该基因中胞嘧啶甲基化导致O6AGTase基因失活引起的。
