Arsenic trioxide (As2O3) inhibits murine WEHI-3 leukemia in BALB/c mice in vivo

Arsenic trioxide (As2O3) is used clinically to treat acute promyelocytic leukemia (APL) and has activity in vitro for induction of apoptosis in several solid tumor cell lines. To investigate the potential therapeutic application of As2O3 for leukemia, we analyzed the effects of As2O3 on the WEHI-3 cells-induced orthotopic leukemia animal model in vivo in this study. We established the WEHI-3 cells leukemia mice through the injection of murine WEHI-3 cells into BALB/c mice, and they were then treated with As2O3 (0.9 and 4.5 mg kg−1; p.o.) and/or combined with all-trans-retinoic acid (ATRA), (30 mg kg−1; i.p.). The results indicated that (1) As2O3 alone or As2O3 combined with ATRA promoted the total survival rate of leukemia mice and these effects are dose-dependent; (2) As2O3 did not affect the body weight but decreased the spleen weight; however, it did not affect liver weight; (3) As2O3 alone or As2O3 combined with ATRA increased the levels of CD3 and CD19, indicating that the differentiation of T and B cells were promoted; and (4) As2O3 alone or As2O3 combined with ATRA did not change the levels of Mac-3 and CD11b markers, indicating that the differentiation of the precursor of macrophage were not inhibited. Based on these observations, As2O3 alone or As2O3 combined with ATRA have efficacious antileukemia activity in WEHI-3 cells leukemia in vivo. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.