Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
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Production of Reactive Oxygen Species and Nitric Oxide by Anticancer Agents in Rat Polymorphonuclear Leukocytes

항암제에 의한 흰쥐 다형핵백혈구의 활성산소종(reactive oxygen species) 및 산화질소(nitric oxide)의 생성

  • Kang, Dong-Joon (College of Veterinary Medicine, Konkuk University) ;
  • Song, Seung-Hee (Changwon College) ;
  • Kim, Cheol-Ho (Livestock Promotion Institute) ;
  • Lee, Sang-Kil (College of Veterinary Medicine (The Institute of Animal Medicine), Gyeongsang National University) ;
  • Kang, Chung-Boo (College of Veterinary Medicine (The Institute of Animal Medicine), Gyeongsang National University)
  • Published : 2009.02.27
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Abstract

The production of reactive oxygen species (ROS) and nitric oxide (NO) by anticancer agents in rat polymorphonuclear leukocytes (PMN) was examined. PMN treated for short term (< or = 4 h) with cyclophosphamide, cisplatin, tamoxifen and doxifluridine, respectively, exhibited an enhanced respiratory burst upon formylmethionylleucy1-phenylalanine (FMLP) stimulation. In the long term (> 4h), the production of ROS was suppressed in a concentration-dependent manner. The production of superoxide anion (${O_2}^-$) from the FMLP-stimulated PMN was enhanced by the treatment (for 1 hr) of cyclophosphamide, cisplatin, tamoxifen and doxifluridine, respectively. While 1 hr-treatment with cyclophosphamide, cisplatin, tamoxifen, and doxifluridine, respectively, suppressed the production of NO from the FMLP-stimulated PMN, while 8 hr-treatment enhanced the production of NO. Neomycin suppressed chemiluminescence in cisplatin-, tamoxifen- and doxifluridine-pretreated PMN, however near suppression of chemiluminescence by ethanol and genistein was observed in PMN pretreated with these agents. Staurosporine and bisindolylmaleimide suppressed chemiluminescence in cisplatin- and doxifluridine- pretreated PMN. Wortmannin has shown a slight suppression in cyclophosphamide-, cisplatin- and tamoxifen-pretreated PMN, but a strong suppression in doxifluridine-pretreated PMN. Methionine strongly suppressed in cyclophosphamide and cisplatin-pretreated PMN. In conclusion, these results indicate that long term treatment of PMN with cisplatin and doxifluridine inhibit respiratory burst through protein kinase C (PKC) translocation, phospholipase C (PLC), D (PLD) and tyrosine phosphorylation kinase (TPK) activation. Tamoxifen inhibits respiratory burst through PLC, PLD, TPK. Cyclophosphamide inhibits respiratory burst through myeloperoxidase (MPO) activity.

항암제에 의해 흰쥐에서 다형핵 백혈구(polymorphonuclear leukocytes, PMN) 의 활성산소종(reactive oxygen species, ROS)과 산화질소(nitric oxide, NO)의 생성변화에 대해 연구하였다. 최근 자극유도인자에 의한 PMN의 호흡방출은 protein kinase C (PKC)의 활성, inositol phosphate transduction pathway의 활성, 그리고 intracellular [$Ca^{2+}$]와 관계가 있다고 밝혀졌으며, 본 연구에서 사용된 항암제(cyclophosphamide, cisplatin, tamoxifen, doxifluridine)중 일부는 화학치료제로써 비특이적으로 면역을 억제하는데 사용되고 있다. 암 치료 시 백혈구의 방어기능에 미치는 영향을 연구하기 위한 목적으로 in vitro에서 각 항암제를 처리한 PMN을 배양하여 ROS와 NO의 생성변화와 이차적 신호전달계인 phospholipase C(PLC), D(PLD), PKC, tyrosine phosphorylation kinase (TPK)와 phosphatidylinositol-3 kinase의 억제율을 측정하였다. PMN에 각각cyclophosphamide, cisplatin, tamoxifen, doxifluridine을 short term(${\leq}4hrs$) 처리시, formylmethionyl-leucy1-phenylalanine (FMLP) 자극에 의해 호흡방출의 증가가 나타났다. 반면, long term (8hrs) 처리 시, ROS의 생성은concentration-dependent 방법으로 감소되었다.

Keywords

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