Pre‐treatment of a human T‐lymphoblastoid cell line with L‐asparaginase reduces etoposide‐induced DNA strand breakage and cytotoxicity

The effect of L‐asparaginase (L‐asp) pre‐treatment on etoposide‐induced DNA strand breakage and cytotoxicity was investigated. In a T‐lymphoblastoid cell line, Molt 4, etoposide‐induced DNA strand breaks, DNA‐protein cross‐links and cytotoxicity were reduced by pre‐treatment with L‐asp for 15 hr, but it did not cause these changes in a promyelocytic‐leukemia 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 [3H]‐etoposide. Cell‐cycle analyses snowed an increase in G1‐phase cells, a significant decrease in both S‐phase cells and G2/M‐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 G2/M‐ phase cells following L‐asp treatment may explain the reduction of etoposide‐induced DNA lesions and cytotoxicity in Molt 4 cells, since topoisomerase‐II (Topo‐II) content or activity is a function of cellular proliferation status.