Kato T, Ohta Y, Suzumura Y, Kohda K, Kimoto H, Kawazoe Y
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya.
Jpn J Cancer Res. 1988 Sep;79(9):1048-53. doi: 10.1111/j.1349-7006.1988.tb00073.x.
The antitumor activity and hematopoietic toxicity of two busulfan analogs were evaluated in comparison with those of busulfan. Although a program of five daily ip treatments with busulfan was not effective in treating sarcoma 180-bearing mice, a fluorine-containing busulfan analog, 1,4-butanediol di-2,2,2-trifluoroethanesulfonate (BFS), and a water-soluble analog, 1,4-butanediol diisethionate (BIT), were significantly effective when given on the same schedule. Busulfan did not appreciably prolong the life span of either P388- or Meth A-bearing mice, whereas BFS and BIT produced significant increases in the life span. It is worth noting that both the analogs were definitely less toxic to the host mice than busulfan. All the drugs examined exhibited suppressive effects on the counts of total WBCs, neutrophils, and lymphocytes. Relative toxicity toward neutrophils versus lymphocytes was increased significantly in the BFS and BIT treatments compared with busulfan treatment. It seems that the toxicity of busulfan in host mice might be due to unidentified side effects other than bone marrow suppression. These results suggest that BFS and BIT could be improved substitutes for busulfan.
评估了两种白消安类似物与白消安相比的抗肿瘤活性和造血毒性。虽然白消安连续5天腹腔注射给药方案对荷肉瘤180小鼠无效，但含氟白消安类似物1,4 - 丁二醇二 - 2,2,2 - 三氟乙烷磺酸酯（BFS）和水溶性类似物1,4 - 丁二醇二乙磺酸酯（BIT）按相同方案给药时具有显著疗效。白消安对荷P388或荷Meth A小鼠的寿命均无明显延长作用，而BFS和BIT能显著延长其寿命。值得注意的是，这两种类似物对宿主小鼠的毒性肯定低于白消安。所有检测药物对白细胞总数、中性粒细胞和淋巴细胞计数均有抑制作用。与白消安治疗相比，BFS和BIT治疗中对中性粒细胞相对于淋巴细胞的相对毒性显著增加。白消安对宿主小鼠的毒性似乎可能是由于除骨髓抑制之外的不明副作用所致。这些结果表明，BFS和BIT可能是比白消安更好的替代药物。
