Co2 laser가 백서의 4-nitroquinoline 1-oxide (4NQO) 유도 구개암에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

CO^^2 Laser는 최근에 두경부 악성종양 및 혈관종등의 절제를 포함하여 난치성 궤양, 점막유두종, 백반증등의 구강 점막질환의 처치등 많은 외과 영역에서 광범위하게 이용되고 있다. 따라서 정상구강조직이나 종양조직에 대한 CO^^2 Laser의 생물학적 영향을 이해하는 것은 중요하다고 사료된다. 그러나 현재까지 종양조직의 제거시 CO^^2 Laser의 생물학적 영향에 대한 연구는 드문 상태이다.

이에 저자는 CO^^2 Laser가 백서의 4NQO유도구개암에 미치는 영향을 연구키 위해, 생후 6주의 Sprague Dawley계 자성 백서 113마리를 1차실험(실험종양유발)의 대조군 15마리 발암군 30마리, 2차실험(Laser조사)의 정상군 33마리, 구개암군 35마리로 구분하여 1차실험에서 propane 1, 2-diol에 희석된 0.5% 4NQO용액을 주3회씩 백서 구개점막에 30주간 반복도포하여 백서 구개암을 유발시킨후, 2차실험에서는 정상구개점막에는 수술도 창상과 Laser창상을, 구개암조직에는 Laser 창상을 형성하여 각 군별로 술후 즉시, 2, 4, 7, 14, 21, 28일째 희생시켜 그 조직 변화를 육안, 광학 및 전자현미경으로 비교 관찰하여 다음과 같은 결론을 얻었다.

1. 발암군은 2-8주에는 경도의 상피증식(acanthosis)만, 10-22주에는 심화되는 상피증식상과 acantholysis 및 상피층의 이형성이, 24주이후에는 잘 분화된 편평상피암의 조직소견이 관찰되었다.

2. 발암군의 전자현미걍적 관찰은 6-10주에는 교소체의 파괴와 세포간극의 확장상을, 10-20주에는 세포질내 공포변성 및 장원섬유의 감소상을, 24주이후의 편평상피암에서는 교소체의 파괴와 세포간극의 확장, 세포질내 공포변성 및 사립체의 종창, 세포질돌기의 결체조직으로의 신장과 기저막 소실, 불규칙한 핵과 세포형태, 뚜렷하고 큰 핵인의 소견을 나타내었다.

3. 정상구개군의 수술도창상은 1주까지 괴사상 및 염증세포침윤, 육아조직 형성을 나타내었으나, 7주째부터는 섬유화되면서 정상결체조직으로 이행된 반면, Laser창상은 초기의 심한 괴사상, 염증세포침윤, 육아조직형성이 3주까지 지속적으로 관찰되었으나 3주째부터 섬유화 소견이 보이기 시작하여 4주째는 정상소견과 유사하였으며, 혈관내 혈전형성이 다양하게 관찰되었다.

4. 구개암군의 Laser 창상은 정상구개군과 마찬가지로 광범위한 괴사를 동반하면서, 혈관내 혈전형성이 관찰되었고, Laser 조사에 의한 암세포의 미세구조적 변화는 관찰되지 않았다.

이와같이 Laser 창상의 치유는 심한 조직괴사와 결체조직의 혈관내 혈전형성으로 수술도창상에 비해 초기에는 치유과정이 지연되었으나 4주후에는 별 차이가 없었으며, 상피층 하부 결체조직의 혈관내 혈전형성은 혈관폐쇄를 야기하므로 CO^^2 Laser에 의한 악성종

양 수술시 암세포의 직접적인 파급을 억제할 것으로 사료된다.

[영문]

The carbon dioxide laser has become more available widely in recent years and is now employed in many blanches of surgery.

It is important to understand the biological effects of CO^^2 laser on normal oral mucosa and tumor tissues so that the likely response in patients can be predicted.

However, little information is available on the biological effects of CO^^2 laser in removing the tumor tissues.

The present study was undertaken to investigate the effects of carbon dioxide laser on 4-nitroquinoline 1-oxide(4NQO) induced palatal carcinoma of the albino rats.

113 albino ruts, Sprague Dawley strain, 6 week old, were used in this experimental study, divided into control group(15) and experimental group(30) in the first experiment(experimental carcirogenesis), then, normal group(33) and cancer group(35) in the second experiment(Laser irradiation).

The first experiment was carried out to produce induced palatal carcinoma by the application of 0.5% 4NQO in propane 1, 2-diol on palatal mucosa of the albino rats three times weekly for 30 weeks.

The animals of experimental group were sacrificed every other week serially after the application of carcinogen.

In the second experiment, CO^^2 laser and blade wounds were orated on normal palatal mucosa while laser wound on the tumor tissues.

All animals were sacrificed serially immediately, 2, 4, 7, 14, 21, 28th day after each wound creation.

The palatal mucosa was excised involving the laser or blade wounds. Tissue was examined grossly, light-microscopically and electron-microscopically.

The obtained results were as follows.

1. In the experimental carcinogenesis for 4NQO induced palatal carcinoma, mild acanthosis only in 2 to 8th week, marked acanthosis with early acantholysis and epithelial dysplasia in 10 to 22th week and well differentiated squamous cell carcinoma in 24 to 30th week were observed light-microscopically.

2. In electron microscopic observation, we observed decrease of desmosomes and widening of intercelluar space in 6 to 10th week of carcinogenesis. Vacuolar degeneration and decrease of tonofilaments in cytoplasm were also seen in 10 to 20th week progressively. Lately, destruction of deamosome, widening of

intercellular space, vacuolar degeneration and swelling of mitochondria in cytoplasm, cytoplasmic process extension with absence of basal lamina, irregular patterns of nucleus and cell features, prominent nucleoli were observed in 24 to 30th week of squamous cell carcinoma.

3. In light microscopic observation of the blade wounds in normal palatal mucosa, necrosis, inflammation and granulation tissue formation were seen until 7th day after would creation but fibrosis and normal connective tissue formation were observed after 1st week, while in the laser wound, more severe necrosis,

inflammation and granulation tissue formation were seen continuously until 3rd week, but fibrosis was seen on 3rd week and similar healing findings compared to blade wound were noted on 4th week. Fibrin thrombi formation was also observed

variably within blood vessels.

4. In the laser wound of palatal carcinoma, its healing process was similar to that in normal palatal mucosa with extensive necrosis and fibrin thrombi within blood vessels, but the ultrastructural changes of tumor cell were not observed.

Specific morphologic changes of the lair wound were extensive tissue necrosis and fibrin thrombi formation within blood vessels of connective tissue mainly, thus delayed healing was prominent in the early stage, but there were no significant differences between laser and blade wound in the later healing process.

It was considered that direct dissemination of the tumor cell was probably inhibited due to vascular occlusion by intravascular thromboses during CO^^2 laser surgery for malignant tumor.