Abstract
本文主旨在研究氯化鎘對中國倉鼠卵巢細胞(Chinese Hamster ovary cells, CHO-K1)的毒性和解毒作用。 Pt4和Pt8 細胞為CHO-K1 長期培養 在含cisplatin 培養基中，為對cisplatin 具有抗性的細胞。Pt8 細胞株 比中國倉鼠卵巢細胞(CHO-K1)對氯化鎘更具抗性，高出約1.3 倍。雖然 Pt4 細胞 GSH含量比K1細胞的高出1.3 倍，但由其對氯化鎘存活率來看， Pt4 細胞比K1細胞對氯化鎘敏感 2.9倍。在未處理藥的情況下，Pt4 細胞 比K1細胞產生微小核球無顯著的差異。Pt8 細胞則和K1細胞微小核產生相 近。在處理0-30 uM 的氯化鎘之後，分析此三種細胞中微小核球產生的量 。發現Pt4 細胞在不同濃度下，均比K1細胞產生較多的微小核球，約高 2.5倍。且由鎘在細胞內分布， Pt4 細胞不論在整個細胞，或者細胞漿液 及細胞核，均累積較多的鎘，約高1.3 倍。由核球沉降速率來看，此三種 細胞分別為Pt8 細胞大於K1細胞大於Pt4 細胞，即Pt4 細胞核球所受的傷 害較大，其次是 K1 細胞。分別給予 K1及Pt4 細胞 4和 8小時修補時間 ，發現 K1 細胞隨修補時間增加，其核球修補能力亦增加。但在Pt4 細胞 中，卻隨修補時間增加，其核球反而受到傷害( 核球沉降速率值較小 )。 檢查Pt4 細胞中，解毒機制有關的酵素，如麩胱甘□酵素 ( glutathione S-transferase )及過氧化氫酵素 ( catalase ) 並沒有明 顯差異。然而，細胞在處理 0-20 uM氯化鎘之後，僅有Pt8 細胞中GSH 的 含量，會隨氯化鎘濃度增加而下降，且有較好的相關性。因此在Pt8 細胞 中，較高的GSH 含量，可解釋對氯化鎘具有抗性的原因。而 Pt4 細胞較 K1 細胞敏感的原因為處理鎘化物後，具有較多鎘累積及較低的修補能力 。 Cisplatin-resistant cells, Pt4 and Pt8 cells, were obtainedom Chinese hamster ovary (CHO-K1) cells after long-term culturecisplatin containing medium. Pt8 cells were about 1.3-foldesistant to cadmium chloride (CdCl2) than CHO-K1 cells. SH content in Pt4 cells was 1.3-fold more than that in4 cells were about 2.9-fold more sensitive to CdCl2after examination with clonogenic survival.20 uM of CdCl2, Pt4 cells were induced aboutmicronucleus than K1 cells were. But Pt8 cellsss micronucleus (about 0.9-fold) than K1 cells were. From nuclear division index, nuclear division in4 cells was inhibited more than that in K1 cells was. Theite results were observed in Pt8 cells (CdCl2 concentration50: K1=20 uM; Pt4=11 uM; Pt8=21.5 uM). In addition,from nucleoid sedimantation assay indicated that the DNAon was significant changed in Pt4 cells after highns of CdCl2 exposure. Also, K1 cells recovered by time dependence after incubatedth fresh medium for 4 or 8 h when treated with CdCl2 for 2 h.Pt4 cells did not recover for 4 or 8 h when treated withfor 2 h. So it seems that Pt4 cells did not recover damagediciently. The detoxfied enzymes, such as catalase,ne S-transferase, and heme oxygenase were nottly different in K1, Pt4 and Pt8 cells. These suggestls were more resistant than K1 cells after exposedmore GSH contents, and Pt4 cells were moreK1 cells after CdCl2 exposure for less reapirmore cadmium accumulation.