温石棉对A549细胞细胞色素P4501 A1和谷胱甘肽S转移酶活性的影响

Effects of chrysotile asbestos on the activities of cytochrome P4501A1 and glutathione S-transferase in A549 cell line

目的 探讨温石棉对体外培养细胞中外源性化合物代谢酶活性的影响。方法 采用不同剂量的UICC温石棉 (UC)和国产茫崖温石棉 (MC)分别作用于A5 4 9细胞 ,测定A5 4 9细胞中细胞色素P4 5 0 1A1(CYP1A1)和谷胱甘肽S转移酶 (GST)活性 ,并用苯并 (a)芘对酶活性进行诱导 ,再测定温石棉对 2种酶诱导活性的影响。结果 UC与A5 4 9细胞作用 2 4h ,乙氧基异酚恶唑 O 去乙基酶 (EROD)活性随剂量增加呈缓慢递增趋势 ,2 0 0mg/LUC可使EROD活性升高 4 0 % ,但 2 0 0mg/LUC作用 4 8h则使其活性下降 32 % ,提示UC对A5 4 9细胞EROD活性的影响呈现低剂量短时间诱导 ,而高剂量长时间抑制的趋势。MC对EROD活性的影响呈现多向性 ,无论作用 2 4h还是 4 8h ,2 5mg/L的MC诱导作用最强 (分别为对照组的 1 86和 1 2 8倍 ) ,但随MC剂量增大和作用时间延长 ,EROD活性也随之下降 ,最低仅为对照组的 35 %。UC作用对GST的影响不明显 ,最高仅使GST活性升高 2 0 %。MC在 2 5mg/L时对GST的诱导最强 ,为对照组的 1 4倍 ,但随着剂量的增加 ,对GST活性的作用由诱导转为抑制 ,2 0 0mg/L时GST活性下降了 18 7%。先用温石棉与A5 4 9细胞作用 2 4h ,再加入苯并 (a)芘对酶活性进行诱导 ,发现无论是UC还是MC ,均未对苯并 (a)

Objective To study the effects of chrysotile on the activities of some enzymes for xenobiotics metabolism Methods UICC chrysotile (UC) and China Mangya chrysotile (MC) asbestos fibers were used at different doses (0, 25, 50, 100, 200 mg/L) to study its effects on the activities of cytochrome P4501A1 and glutathione S transferase (GST) in A549 cell line Also, the effects of chrysotile on the activities of CYP1A1 and GST induced by benzo(a)pyrene were studied Results The activity of EROD increased slowly with the increasing dose of UC, as A549 cells were incubated with UC for 24 h, and EROD activity increased by 40% at a dose of 200 mg/L UC However, activity of EROD decreased by 32% with 48 h incubation at the same dose, indicating that lower dose of UC and short time could induce the activity of EROD in A549 cells, whereas higher doses and long time could inhibit its activity MC exhibited a multiphasic effects on the activity of EROD, whether at a dose of 25 mg/L for 24 h or 48 h all gave the strongest induction, 1 86 times or 1 28 times as controls, respectively However, EROD activity decreased with the increases in MC doses and incubation time, with the lowest as 35% of the controls The effect of UC on GST activity was not so obvious, with the highest as the increase in its activity by 20% The highest induction of MC to GST activity was at a dose of 25 mg/L, 2,5 times as that in controls With the increases in its doses, effects of MC on GTS activity became inhibition from induction, like that on EROD activity MC at a dose of 200 mg/L could lower the activity of GST by 18 7% A549 cells were incubated with chrysotile fiber for 24 h firstly, and then incubated with benzo(a)pyrene to induce the activities of EROD and GST The results showed that neither UC nor MC could affect the activity of EROD induced by benzo(a)pyrene However, UC at a dose of 200 mg/L and MC at 100 mg/L could increase the activity of GST induced by benzo(a)pyrene Conclusion Chrysotile at different doses or its different types showed varied effects on the activities of EROD and GST in A549 cell lines, probably because of different physicochemical characteristics and surface activity of two kinds of asbestos