Cis-Dichlorodiammineplatinum이 Mouse 간장의 인산염 분해효소활성에 미치는 영향 = Effect of Cis-Dichlorodiammineplatinum on the Phosphatase Activities of Liver in Mice

국문 초록 (Abstract)

cis-Dichlorodiammineplatium(Ⅱ)(cis-DDP)은 최근에 개발된 효과적인 종양화합 요법제인 금속화합물로서 그 작용기작은 아직 불명하나 bifunctional alkylating agent와 유사한 작용 기전을 갖는 것으로 알려져 있다.
cis-DDP는 체내에서 가수분해되어 DNA와 반응함을 핵산의 합성을 억제하여 암세포 뿐만 아니라 정상세포에도 영향을 미쳐 출혈성장염, 임파조직과 골수의 저세포증, 신손상, 단백뇨 및 혈뇨등의 부작용을 유발한다. 이에 저자는 cis-DDP가 mouse 간장에서 세포독성으로 작용하여 간실질세포의 변성을 일으키리라 사료되어 간실질세포내의 acid phosphatase, alkaline phosphstase 및 aden-osine triphosphatase의 변동을 조직화학적으로 관찰하였다. 실험동물은 DDY계의 웅성(체중 20g)mouse를 사용하였으며 체중 kg당 6mg의 cis-DDP를 투여한 후, 6시간, 12시간, 24시간 및 48시간 경과후에 희생하여 간조직을 적출하고 10% formalin용액에 고정하고 cryostat로 16㎛두께로 동결절편을 만들었다. 조직화학적인 연구를 위하여 acid phosphatase와 alkaline phosphatase의 활성은 Gomori 방법으로 그리고 adenosine triphosphatase의 활성은 Wachstein-Meisel 방법으로 이들 효소활성을 관찰하여 다음과 같은 결과를 얻었다.
1. Acid phosphatase 활성은 간소엽주변대에서 cis-DDP투여 6시간 경과군의 mouse에서는 약한 양성반응을 12시간 경과군의 mouse에서는 중등도의 양성반응을 48시간 경과군의 mouse에서는 약한 양성반응을 나타내었다.
2. Alkaline phosphatase 활성은 간소엽 주변대에서 cis-DDP투여 12시간, 24시간, 및 48시간 경과군의 mouse에서 중등도의 양성반응을 나타내었다.
3. Adenosine erihosphatase 활성은 간소엽 중심대에서 cis-DDP투여 6시간 경과군의 mouse에서 미약한 양성반응을 나타내었고, 12시간 경과군의 mouse에서는 중등도의 양성반응을 나타내었고, 24시간 및 48시간 경과군의 mouse에서는 각각 중등도 및 강한 양성반응을 나타내었다.
이상의 소견을 종합한바 cis-DDP의 투여로 mouse의 간장 손상을 일으켜 acid phosphstase, alkaline phospatase 및 adenosine triphosphatase 활성은 일시적으로 저하되었다가 회복되는 것으로 사료된다.

다국어 초록 (Multilingual Abstract)

cis-Dichlorodiammineplatinnm(Ⅱ) (cis-DDP), known as cisplatin, is a metallic compound that has recently been developed as an effective cancer chemotherapeutic agent. The precise mechanism of action of cis-DDP is still unknown. Similarities between the mechanism of action of this drug and bifunctional alkylating agents have been suggested. Upon entering the cell, the platinum compounds will become hydrolyzed, and then they can react with DNA. They act on tumor cells as well as normal cells. Side effects included severe hemorrhagic enterocolitis, severe hypocellularity of the bone marrow and lymphoid tissues, renal lesions, proteinuria and (microscopic henaturia).
In this experiment, the author studied the effect of cis-DDP on the mouse liver, histochemically observing the changes in the activities of acid phosphatase, alkaline phosphatase, and adenosine triphosphatase. Male mice (the weight 20g), DDY strain, were used as experimental animals. The experimental animals were sacrificed at 6,12,24 and 48 hours after administration of 6mg of cis-DDP per kilogram of body weight. The specimens obtained from the liver were fixed in 10% formalin solution and sliced at 16㎛ thickness in a frozen cryostat. The activities of acid and alkaline phosphatases were observed by the Gomori's method and the activity of adenosine triphosphatase was observed by the Wachstein Meisel's method for histochemical study.
The results are as follows.
1. The acid phosphatase activity was weakly positive at 6 hours and moderately positive at 12 hours and weakly positive at 48 hours after administration in the peripheral zone of the hepatic lobule.
2. The alkaline phosphatase activity was decreased to moderately positive at 12,24 and 48 hours after administration in the peripheral zone of the hepatic lobule.
3. The adenosine triphosphatase activity was trace positive at 6 hours after administration in the central zone of the hepatic lobule and moderately positive at 12 hours after admnistration in the central and peripheral zone of the hepatic lobule.
It is suggested that cis-DDP causes changes in activities of acid phosphatase, alkaline phosphatase and adenosine triphophsatase in the liver, due probably to the cytotoxic effect in the parenchymal cells of the liver in mice.