Kondrat'eva N A, Dobrynin Ia V, Merkulov M F
Antibiotiki. 1977 Nov;22(11):994-8.
L-Asparaginase sensitivity and asparagin-deficiency of 5 tumor cell populations, i.e. mouse lymphoma L-1210, LI0-1, LTL, Berkitt lymphoma and human ovary cancer, line CaOv were studied. Radiometric estimation of 3H-thimidine incorporation into the cells of DNA served a criterion of cytotoxicity. "Krasnitin" (FDR) was used as L-asparaginase. The cells of leukemia L-1210, lymphosarcoma LIO-1 and line CaOv were asparagine-independent and non-sensitive to L-asparaginase. The cells of mouse lympholeukemia LTL and the cultures of Berkitt human lymphoma proved to be asparagin-dependent and highly sensitive to L-asparaginase. In concentration of 50 IU/ml the drug inhibited incorporation of 3H-thimidine in the cells of LTL and Berkitt lymphoma by 97-98 and 75-80 per cent respectively. Inhibition of 3H-thimidine incorporation in the cells of LTL and Berkitt lymphoma was more pronounced after incubation with the drug for 8 and 24 hours respectively. Two out of the 5 tumor cell populations were chosen as a result of the study. One of these 2 populations, i.e. the cells of Berkitt lymphoma was asparagin-dependent and highly sensitive to L-asparaginase, the other, i.e. the cells of line CaOv was asparagin-independent and resistant to the specific antitumor effect of the enzyme. The use of a system of these two cell lines provided estimation of the ratio of the specific cytostatic (antitumor activity) and non-specific cytostatic properties in the preparations with L-asparaginase activity.
研究了5种肿瘤细胞群体,即小鼠淋巴瘤L - 1210、LI0 - 1、LTL、伯基特淋巴瘤和人卵巢癌CaOv细胞系对L - 天冬酰胺酶的敏感性及天冬酰胺缺乏情况。以放射性测定法检测3H - 胸腺嘧啶掺入细胞DNA的情况作为细胞毒性的标准。使用“克拉西丁”(FDR)作为L - 天冬酰胺酶。白血病L - 1210细胞、淋巴肉瘤LIO - 1细胞和CaOv细胞系对天冬酰胺不依赖,且对L - 天冬酰胺酶不敏感。小鼠淋巴细胞白血病LTL细胞和伯基特人淋巴瘤培养物对天冬酰胺依赖,且对L - 天冬酰胺酶高度敏感。在50 IU/ml浓度下,该药物分别抑制LTL和伯基特淋巴瘤细胞中3H - 胸腺嘧啶掺入97% - 98%和75% - 80%。分别在与药物孵育8小时和24小时后,LTL和伯基特淋巴瘤细胞中3H - 胸腺嘧啶掺入的抑制更为明显。研究结果选取了5种肿瘤细胞群体中的2种。这2种群体中的一种,即伯基特淋巴瘤细胞对天冬酰胺依赖,且对L - 天冬酰胺酶高度敏感;另一种,即CaOv细胞系对天冬酰胺不依赖,且对该酶的特异性抗肿瘤作用具有抗性。使用这两种细胞系组成的系统可评估具有L - 天冬酰胺酶活性的制剂中特异性细胞生长抑制(抗肿瘤活性)和非特异性细胞生长抑制特性的比例。