Sadiq M F, Zaghal M H, El-Shanti H E
Department of Biological Sciences, Yarmouk University, Irbid, Jordan.
Mutagenesis. 2000 Sep;15(5):375-8. doi: 10.1093/mutage/15.5.375.
The genotoxicity of the rhodium(III) complex cis-[Rh(biq)(2)Cl(2)]Cl (complex R) in cultured human lymphocytes was studied using the chromosome aberrations (CAs) assay. Lymphocyte cultures were initiated from two adult healthy non-smoking male volunteers and were exposed to the complex for a duration of 3 or 20 h prior to cell collection. The reduction in mitotic indices (MI) and the induction of CAs represented the toxic and clastogenic effects of the different treatments, respectively. Complex R proved to be an intermediate toxic clastogen with a MI(50) of 1.0 microg/ml and a minimum positive dose (MPD) of 0.1 microg/ml. Like bleomycin, complex R exerted its clastogenic effects without the need for metabolic activation and induced CAs of all types in lymphocytes treated in the G(2) and late S phases and, therefore, can be considered a radiomimetic. In addition, it induced more total CAs of chromatid-type than of chromosome-type. The reduction in the frequencies of CAs following the 20 h treatment as compared with those induced following the 3 h treatments indicated that human lymphocytes in the presence of complex R can partially tolerate the lesions involved in CA production. Based on the biological effects of complex R and the similarities between its functional group and that of bleomycin, possible mechanisms for complex R genotoxicity are discussed.
采用染色体畸变(CA)试验研究了铑(III)配合物顺式-[Rh(biq)₂Cl₂]Cl(配合物R)对培养的人淋巴细胞的遗传毒性。淋巴细胞培养物取自两名成年健康不吸烟男性志愿者,在收集细胞前将其暴露于该配合物中3或20小时。有丝分裂指数(MI)的降低和CA的诱导分别代表了不同处理的毒性和致断裂效应。配合物R被证明是一种中度毒性的致断裂剂,其MI₅₀为1.0微克/毫升,最小阳性剂量(MPD)为0.1微克/毫升。与博来霉素一样,配合物R无需代谢激活即可发挥其致断裂作用,并在G₂期和S期后期处理的淋巴细胞中诱导所有类型的CA,因此可被视为一种拟辐射剂。此外,它诱导的染色单体型总CA比染色体型更多。与3小时处理后诱导的CA频率相比,20小时处理后CA频率的降低表明,在配合物R存在的情况下,人淋巴细胞可以部分耐受CA产生过程中涉及的损伤。基于配合物R的生物学效应及其官能团与博来霉素官能团的相似性,讨论了配合物R遗传毒性的可能机制。