鲁吡替康致突变性研究

Study on the Mutagenesis of Rubitecan

背景与目的:研究鲁吡替康(9NC)的致突变作用。材料与方法:采用微核实验,研究9NC体外对人淋巴细胞和体内对小鼠骨髓嗜多染红细胞(polychromatic erythrocytes,PCE)的诱变作用;采用小鼠抑瘤实验,研究9NC对小鼠移植瘤S180和Heps的肿瘤抑制作用。结果:9NC分别在体外≤0.187μg/ml及体内≤0.375mg/kg剂量范围内,不诱发人淋巴细胞微核和小鼠骨髓PCE微核的增加(P>0.05),但对小鼠移植瘤S180(肉瘤)和Heps(肝癌)有抑制作用;在剂量≥0.25μg/ml(体外)和≥0.75mg/kg(体内)时,9NC可引起人外周血淋巴细胞微核和小鼠骨髓PCE微核的显著增加(P<0.01),有明显的遗传毒性。结论:9NC在最大安全耐受剂量内具备致突变性。

BACKGROUND ＆ AIM： To study the mutagenesis of Rubitecan （9NC）. MATERIALS AND METHODS： The micronucleus test in human lymphocytes （in vitro ） and in bone marrow PCE of mice （in vivo） were used. Induction of transplantated tumor in mice with 9NC was observed. RESULTS： 9NC had no mutagenicity in human lymphocytes within 0-0. 187μg/ml and no mutagenicity to murine bone marrow PCE within 0-0.375 mg/kg body weight （P 〉 0.05）, but could inhibit the growth of transplantated tumor Hpes （heptome） and S180 （sarcoma） in mice. Mutagenic effects of 9NC was found with dosages of ≥0.25 μg/ml （in vitro） and ≥0.75 mg/kg body weight （in vivo）. CONCLUSION： 9NC demonstrated mutatgenic effects at different dose ranges.