乙醛與鎘(II),鉛(II),鉻(VI)等金屬離子對中國倉鼠肺臟細胞複合毒性之探討

由於台灣地區地狹人稠，對於環境衝擊耐受之程度較低。因此， 本土環 境污染不但會破壞生態平衡，更極易對人體健康形成危害。由於人類環境 周遭往往不僅只有暴露一種環境毒物，有時會有兩種或兩種以上的環境污 染物。為了瞭解這些環境毒物彼此之間對於生物的影響，是否具有交互作 用，進而影響細胞的存活或造成細胞基因突變。關於這些環境毒物彼此之 間的交互作用，在目前文獻中的研究較少。 故本實驗以V79細胞(中國倉 鼠肺臟細胞)為研究對象， 探討乙醛和重金屬化合物對於細胞毒性及基因 毒性之複合效應。 以下列三種型式來探討; 高劑量的短期暴露4小時(乙 醛 2.5-20.0mM; 氯化鎘12.5 - 2 0 0μ M; 氯化 鉛: 0.25-2.00mM; 重 鉻酸鉀: 4- 32μ M )和低劑量長時間暴露72小時(乙醛250 - 1000μ M ;氯化鎘: 1.25 - 10.00μ M ; 氯化鉛: 12.5- 100.0μ M ; 重鉻酸鉀: 3.2-0.4μ M ) 及持續性暴露乙醛及此三種重金屬化合物對 於V79細胞產生之效應。 除了研究這兩種毒物單一暴露及兩者複合暴露對 於細胞存活率及細胞對Alamar blue代謝活性的影響， 另外對於hprt ( hypoxanthine phosphoribosyl transferase)基因突變的效應進行研究。 由結果顯示可知細胞存活率及細胞代謝活性， 均隨著毒物劑量的增加而 下降(p<0.05)，而hprt基因突變率亦隨之上升(p<0.05).在相同細胞毒性 濃度時，複合暴露此兩種毒物，除了細胞存活率及細胞代謝活性比單一相 同細胞毒性濃度的毒物下降外， hprt基因突變率更顯著上升。則當此兩 類毒物共同暴露時，對V79細胞之細胞毒性及基因毒性均有顯著之加成性 。 最後隨著持續性低劑量的毒物暴露次數的增加， V79細胞對於毒物的 耐受性明顯增加(P<0.05) ， 而且細胞突變數目亦顯著增加(P<0.05) 。 我們也討論到暴露於這些重金屬污染的作業廠工人， 若有酗酒的習慣或 同時暴露於含有乙醛的環境中， 則對於人體有加成性的傷害。

As a crowdly living place, Taiwan is highly populated and is thus sensitivelyto environmental hazard. Therefore, the emissions of the pollutant has not only disrupted the balance of environment but also cause severse hazard to human being. According to literature, most have studied on the toxicity of singlechemical. However, considering the fact that human exposure to multiple paths and varietal chemicals, the biological combination or synergistic/antagonistic effect is necessary to investigate. To understand the interaction between biological system and cytotoxicity or genotoxicity, we have forcused on thechemical mixtures in vitro test. By exposure V79 cell line in vitro to acetaldehyde, Cadmium Chloride, Lead Chloride and Potassium Dichromate , a series of test has been used to investigate these agents which act as synergistic / independent or cumulative ofeach other in producing cytotoxicity or genotoxicity. Three pattern of exposing interval has been proceeded, high dosage in shot interval (4 hours, Acetaldehyde12.5~20mM, Cadmium Chloride 2 0 0μM , Lead Chloride 0.25-2.00mM, Potassium Dichromate 4-3.2μ M ) and long interval at low dosage (72 hours , Acetaldehyde250 - 1000μ M ;Cadmium Chloride 1.25 - 10.00μ M , Lead Chloride 12.5-100.0μ M ; Potassium Dichromate 0.4- 3.2μ M ). In order to see the cumulativeeffect of toxic agent, third exposing pattern has been proceeded by introducingthe agent from 1 to 3 times to the cell. Each exposure has been left enough time to incubate and rejustify the cell number. Our studies has shown that V79 cells reduced its viability and metabolicactivity as the dose of exposure increase. One of the claslogenic indicator hprtgene (hypoxanthine phosphoribosyl transferase) mutation ratio increase ,evenexposing dose the additive synthetic effect has bound V79 cell exposure toacetaldehyde and these metals . As the elevation continously exposure number, the enhancement of V79 cell tolerence has been observed , and the hprt gene mutation ratio also increase.As the acetaldehyde is the major metabolic inter-mediate of alcohol in human body, the dietary and occupational intake of acet-aldehyde have mixed exposure to a number of metalic compounds give rise to thecytotoxicity and genotoxicity.