Transfectant CHO cells expressing O6-alkylguanine-DNA-alkyltransferase display increased resistance to DNA damage other than O6-guanine alkylation.
Transfectant CHO cells expressing O6-alkylguanine-DNA-alkyltransferase display increased resistance to DNA damage other than O6-guanine alkylation.
复制标题
表达O6-烷基鸟嘌呤-DNA-烷基转移酶的转染CHO细胞表现出对O6-鸟嘌呤烷基化以外的DNA损伤的更强的抵抗力。
DOI：
10.1093/carcin/8.12.1853
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发表时间：
1987
期刊：
影响因子：
4.7
通讯作者：
Paxton,MB
中科院分区：
文献类型：
--
作者：
Barrows,LR;Borchers,AH;Paxton,MB
BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea, Carmustine] is a nitrosourea that crosslinks DNA and is useful in cancer chemotherapy. Tumor cells resistant to BCNU produce high levels of O6-alkylguanine-DNA-alkltransferase (AT), a protein that removes the O6-guanine adduct formed by BCNU prior to crosslinking. By the transfection of a human cosmid library into the Chinese hamster ovary cell line AA8, several transgenic cell lines which express the AT gene have been constructed. These ‘BR’ cells were isolated on the basis of their resistance to G-418 and BCNU. Like human mer+strains, BR cells (relative to the parental AA8 cells) are ˜500 times more resistant to the cytotoxic effects of 80 μM BCNU. Treatment with exogenous O6-methylguanine (O6MG), which depletes cellular AT, abolishes their BCNU resistance. Also consistent with the mer+phenotype, BR cells are resistant to the mutagenic and killing activity ofN-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Treatment with exogenous O6MG, while reversing the resistance to MNNG mutation, does not reverse the resistance to MNNG killing. Unexpectedly, BR cells also exhibit resistance to killing by dimethylsulfate (DMS). The BR cells are not, however, detectably resistant to UV light. These results suggest that AT activity in mammalian cells is dosely linked to the activity of other DNA repair pathways.
