Pre-treatment of a human T-lymphoblastoid cell line with L-asparaginase reduces etoposide-induced DNA strand breakage and cytotoxicity
✍ Scribed by Tsunehiro Shimizu; Masaru Kubota; Souichi Adachi; Hirohiko Sano; Yasufumi Kasai; Hisako Hashimoto; Yuichi Akiyama; Haruki Mikawa
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- French
- Weight
- 480 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The effect of L-asparaginase (L-asp) pre-treatment on etoposide-induced DNA strand breakage and cytotoxicity was investigated. In a 1-lymphoblastoid cell line, Molt 4, etoposideinduced DNA strand breaks, DNA-protein cross-links and cytotoxicity were reduced by pre-treatment with L-asp for I 5 hr, but it did not cause these changes in a promyelocyticleukemia cell line, HL-60, which is less sensitive than Molt 4 to L-asp. However, pre-treatment of Molt 4 cells with L-asp did not significantly alter the accumulation of ['HI-etoposide. Cell-cycle analyses showed an increase in G,-phase cells, a significant decrease in both S-phase cells and GJM-phase cells pre-treated with L-asp in Molt 4 cells, but L-asp exposure did not result in any significant changes in HL-60 cells. On the other hand, L-asp pre-treatment did not affect topoisomerase-I (Topo-I) inhibitor, camptothecin (CPT)-induced DNA strand breaks or toxicity in Molt 4 cells. Our data imply that a decrease in S-and GJMphase cells following L-asp treatment may explain the reduction of etoposide-induced DNA lesions and cytotoxicity in Molt 4 cells, since topoisomerase-ll (Topo-ll) content or activity is a function of cellular proliferation status.