Effect of Administration Styles of Arsenic Trioxide on the Intracellular Arsenic Concentration and the Efficiencies of Differentiation and Apoptosis.

Objective: Study on the effects of As₂O₃ on intracellular arsenic concentration, differentiation and apoptosis rates and sensitivities by different administration styles.

Methods: Evaluated the intracellular arsenic concentrations,the apoptosis rates, and the ratios of differentiation phenotypes on cell surface CD33 (−)/CD11b (+), when incubated cells with As₂O₃ in different culture media in vitro and treated leukaemia patients with As₂O₃ in different administration styles in vivo.

Results: When incubated cells in a constant arsenic concentration culture medium for 24 hours, the intracellular arsenic concentrations were (33.4±0.88) μg/L in NB₄, (18.6±1.12) μg/L in K₅₆₂, and (28.8±0.64) μg/L in APL; the apoptosis rates were NB₄ 56.6%, K₅₆₂ 27.6%, APL 52.2%; the ratios of differentiation phenotype CD33(−)/CD11b(+) were: NB₄ (19.5±0.5)%, K₅₆₂ (24.5±0.6)%, APL (18.5±0.6)%, whereas, when incubated cells above in a changing arsenic concentrations culture medium for 24hours, which initial arsenic level was 5μmol/L, the intracellular arsenic concentrations were: NB₄(17.6±0.88) μg/L, K₅₆₂(9.2±0.64)μg/L, APL(15.2±1.04)μg/L, the apoptosis rates were: NB₄ 23.2%, K₅₆₂ 11.0%, APL 21.0%; the ratios of differentiation phenotype CD33 (−)/CD11b (+) were: NB₄ (51.5±0.4)%, K₅₆₂ (57.5±0.8)%, APL (46.5±0.5)%. 24hours after one time continuous and slowing intravenous As₂O₃ infusion, the intracellular arsenic concentrations were APL (26.6±2.5) μg/L,AML-M₂ (15.5±3.1) μg/L, CML (18.5±2.3) μg/L; the apoptosis rates were APL 28.5%, AML-M₂ 9.5%, CML 12.5%; the ratios of differentiation phenotype CD33 (−)/CD11b (+) were: APL (29.5±0.5)%, AML-M₂ (28.5±0.6) %, CML (23.5±0.5)%. Whereas, when 24hours after treated with one time general speed intravenous As₂O₃, the intracellular arsenic concentrations were: APL(12.3±2.1) μg/L, AML-M₂ (5.5±2.3) μg/L, CML (8.5±2.7) μg/L; the apoptosis rates were: APL 13.2%, AML-M₂ 3.9%, CML4.2%; the ratios of differentiation phenotype CD33 (−)/CD11b (+) were: APL (53.6±0.8) %, AML-M₂ (48.5±0.9) %, CML (67.5±0.8) %.

Conclusions: The administration styles affect the intracellular arsenic concentrations, the differentiation rates and the ratios of apoptosis of leukaemia cells. Treated with the continuous and slowing intravenous As₂O₃ infusion can obtain a higher intracellular arsenic concentration, a higher efficiency of apoptosis and a lower differentiation ratio than that in general speed intravenous As₂O₃ infusion in clinical dosage. The continuous and slowing intravenous As₂O₃ infusion can promote apoptosis and inhibit from differentiation, so this As₂O₃ medication can relieve leukocytosis and elevate therapeutic effects.