Mourelatos C, Nikolaropoulos S, Fousteris M, Pairas G, Argyraki M, Lykidis D, Fidani S, Mourelatos D, Lialiaris Th
Laboratory of Genetics, Medical Faculty, Demokritos University of Thrace, Alexandroupolis 68100, Greece.
Laboratory of Pharmaceutical Chemistry, University of Patras, Greece.
Mutat Res Genet Toxicol Environ Mutagen. 2014 May 15;766:42-5. doi: 10.1016/j.mrgentox.2014.03.005. Epub 2014 Mar 25.
We studied the effects of three newly synthesized steroidal derivatives of nitrogen mustards, alone or in combination with caffeine, on sister chromatid exchange (SCE) frequencies and on human lymphocyte proliferation kinetics. The agents have as alkylator functionalities either P-N,N-bis(2-chloroethyl)aminophenyl-buturate (CHL) or P-N,N-bis(2-chloroethyl)aminophenyl-acetate (PHE), esterified with a modified steroidal nucleus. An enhancement of SCE frequency was seen with compounds which contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17-position of the D-ring. The exocyclic insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) gave a compound showing increased SCE frequency. Enhanced cytogenetic damage was observed when lymphocytes were exposed in vitro to caffeine. The compounds, alone or in combination with caffeine, caused a concentration-dependent increase in SCE frequencies and cell division delays, and caffeine was found to act synergistically with the steroidal alkylators.
我们研究了三种新合成的氮芥甾体衍生物单独或与咖啡因联合使用对姐妹染色单体交换（SCE）频率和人淋巴细胞增殖动力学的影响。这些试剂具有作为烷化剂功能的P-N，N-双（2-氯乙基）氨基苯基丁酸酯（CHL）或P-N，N-双（2-氯乙基）氨基苯基乙酸酯（PHE），它们与修饰的甾体核酯化。含有PHE或CHL作为烷化剂并与在D环的17位添加了胆甾烯基的甾体核酯化的化合物可使SCE频率增加。在甾体核的D环中用PHE酯化的-NHCO-基团的环外插入（PHE的酰胺酯）得到一种显示SCE频率增加的化合物。当淋巴细胞在体外暴露于咖啡因时，观察到细胞遗传损伤增强。这些化合物单独或与咖啡因联合使用会导致SCE频率和细胞分裂延迟呈浓度依赖性增加，并且发现咖啡因与甾体烷化剂具有协同作用。
