Andrulis I L, Argonza R, Cairney A E
Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Somat Cell Mol Genet. 1990 Jan;16(1):59-65. doi: 10.1007/BF01650480.
Human cell lines resistant to L-asparaginase or albizziin were isolated by multistep selection of HT1080 fibrosarcoma and MIA PaCa-2 pancreatic carcinoma cells. Mutants were cross-resistant to both drugs, but more resistant to the drug used for selection. The drug-resistant cell lines expressed elevated levels of asparagine synthetase activity and protein, up to 17-fold over that of the parental cells. Enzyme overproduction was due to gene amplification in the albizziin-resistant cells, whereas increased expression without amplification was observed in L-asparaginase-resistant cells.
通过对HT1080纤维肉瘤细胞和MIA PaCa-2胰腺癌细胞进行多步筛选，分离出了对L-天冬酰胺酶或合欢氨酸具有抗性的人细胞系。突变体对两种药物均具有交叉抗性，但对用于筛选的药物抗性更强。耐药细胞系中天冬酰胺合成酶活性和蛋白水平升高，比亲代细胞高17倍。在合欢氨酸耐药细胞中，酶的过量产生是由于基因扩增，而在L-天冬酰胺酶耐药细胞中观察到无扩增情况下表达增加。
