Weissberg J B, Herion J C, Walker R I, Palmer J G
Cancer Res. 1978 Jun;38(6):1523-7.
Cycloheximide (CHM), a potent inhibitor of protein synthesis, has been reported to protect rat intestinal crypt cells from mitotic inhibition by nitrogen mustard (HN2). For investigation of the effect of CHM on the bone marrow toxicity of HN2, CHM (1.0 mg/kg) and HN2 in doses up to 2.5 mg/kg were given i.p. to rats. Twenty-eight % (13 of 46) of rats given HN2 alone died within 5 days. Only 4% (2 of 45) of rats pretreated with CHM died within 5 days after the administration of HN2. Rats pretreated with CHM had significantly less leukopenia and granulocytopenia than did rats given HN2 alone, and their bone marrow cellularity, assessed by histological sections and total femoral marrow cell counts, was greater than that of animals given HN2 alone. Bone marrow DNA synthesis, as measured by in vitro [3H]thymidine incorporation, was decreased 2 hr after HN2 injection, appeared to recover at 4 hr, but was further decreased at 24 and 48 hr. CHM given up to 20 min before HN2 reversed the effect of HN2 on DNA synthesis at 2 and 4 hr. A variable protective effect of CHM was observed at 24 and 48 hr. These studies indicate that CHM increases the survival of HN2-treated rats and partially protects rat bone marrow cells from HN2 cytotoxicity.
放线菌酮（CHM）是一种有效的蛋白质合成抑制剂，据报道它能保护大鼠肠道隐窝细胞免受氮芥（HN2）的有丝分裂抑制作用。为了研究CHM对HN2骨髓毒性的影响，将CHM（1.0毫克/千克）和剂量高达2.5毫克/千克的HN2腹腔注射给大鼠。单独给予HN2的大鼠中有28%（46只中的13只）在5天内死亡。在给予HN2后5天内，预先用CHM处理的大鼠中只有4%（45只中的2只）死亡。预先用CHM处理的大鼠白细胞减少和粒细胞减少明显少于单独给予HN2的大鼠，通过组织学切片和全股骨骨髓细胞计数评估，其骨髓细胞密度高于单独给予HN2的动物。通过体外[3H]胸腺嘧啶核苷掺入法测量，骨髓DNA合成在HN2注射后2小时减少，在4小时似乎恢复，但在24小时和48小时进一步减少。在HN2注射前20分钟给予CHM可逆转HN2在2小时和4小时对DNA合成的影响。在24小时和48小时观察到CHM有不同程度的保护作用。这些研究表明，CHM可提高HN2处理大鼠的存活率，并部分保护大鼠骨髓细胞免受HN2的细胞毒性作用。
