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Hamster 협낭점막 DMBA-유도구강상피암의 二相발암과정 (Two-phase carcinogenesis)에 관한 세포학적 연구

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 (The) histopathological study on two-phase carcinogenesis of DMBA-induced oral carcinoma in hamster buccal pouch 
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저자는 구강상피암의 二相발암과정(two-phase carcinogenesis)의 실험적 증명과 초기발암과정에 관한 연구를 위해 생후6주된 Golden Syrian Hamster의 협낭점막에 heavy mineral oil로 희석된 9,10-dimethyl-1,2-benzanthracene(DMBA)를 주당 3회 도포하여, 통법의 0

.5% DMBA용액에 의한 암 발생군(실험 Ⅰ군), 0.1% DMBA용액에 의한 발암개시군(실험 Ⅱ군), 0.1% DMBA용액에 의한 발암개시후 같은 농도에 의한 발암증진군(실험Ⅲ군), 0.1% DMBA용액에 의한 발암개시후 0.5% DMBA용액에 의한 발암증진군(실험Ⅳ군)의 시기별 조직변화

과정을 육안·광학현미경 및 전자현미경상에서 비교 관찰하여 다음과 같은 결론을 얻었다.

1. 0.5% DMBA용액에 의한 암 발생군인 실험 Ⅰ군에서는 과각화증, 분화 및 미분화 상피세포의 증식, 이형성, 유두종양증식, 상피내암 및 침윤성상피암이 관찰되었으며 최초의 암발생 시기는 8주째였다.

2. 0.1% DMBA용액에 의한 발암개시군인 실험 Ⅱ군에서는 과각화증과 분화 및 미분화 상피 세포의 증식만 보였다.

3. 0.1% DMBA용액의 도포 완료 후 6주간의 실험 Ⅱ군에서 광학현미경상에서는 특기할 변화가 없었으나 전자현미경상에서는 핵의 증대, 세포간격의 확장 및 기저막의 불규칙상등의 계속적인 변화를 보였다.

4. 0.1% DMBA 용액에 의한 발암증진군인 실험 Ⅲ군에서는 과각화증, 분화 및 미분화 상피세포의 증식, 이형성 및 유두종양증식등을 보였고, 9주째에 상피내암도 관찰되어 실험 Ⅳ군보다는 현저한 세포변화를 보였으나 실험 Ⅳ군에 비하여는 현저하지 않았다.

5. 0.5% DMBA용액에 의한 발암증진군인 실험 Ⅳ군은 실험 Ⅰ군에 비해 이형성, 상피내암 및 침윤성상피암의 발현이 약 2주정도 빨랐으며 미분화 상피세포의 증식이 보다 현저하였다.

이상의 결과를 종합하면 구강상피암의 발생과정에도 발암개시상(initiation phase)과 발암증진상(promotion phase)의 二相발암과정이 확실히 존재하고, 발암개시상에 분명한 세포변화가 존재하며, 그 변화과정은 발암개시상의 발암잠재력 및 불가역적 세포변화를 시사한다고 사료되는 바이다.


Studies related to two-phase mechanism of carcinogenesis have been rarely carried out on oral mucosa.

The present study was undertaken to investigate the histopathological and ultrastructural changes during two-phase carcinogenesis of 9,10-Dimethyl-1,2-Benzanthracene (DMBA)induced oral carcinoma on the mucosa of hamster buccal pouch.

The purposes of this study were to demonstrate two-phase mechanism of chemical carcinogenesis on oral mucosa, and to investigate histopathological changes on early potential changes of oral carcinoma.

Golden Syrian Hamsters-6 week old-were used in this experimental study, and divided into control and four experimental groups, and experimental groups were painted with DMBA in heavy mineral oil on left buccal pouch three times weekly as follows:

Experimental Group Ⅰ(32): Painting with 0.5 % DMBA for 16 weeks.

Experimental Group Ⅱ(32): Painting with 0.1% DMBA for 10 weeks, no-treatment for a following 6 week period.

Experimental Group Ⅲ(20): Painting with 0.1% DMBA for 10 weeks after prior treatment as Group Ⅱ.

Experimental Group Ⅳ(20): Painting with 0.5% DMBA for 10 weeks after prior treatment as Group Ⅱ.

The animals were sacrificed every week serially, and chemical-treated buccal mucosae were excised and examined grossly, light-microscopically and electron-microscopically. The obtained results were as follows.:

1. In Group Ⅰ, hyperkeratosis, squamoid (differentiated) and basaloid (undifferentiated) epithelial hyperplasia, dysplasia, papillomatous growth, carcinoma in situ, and invasive carcinoma were all seen on light microscope. Early carcinoma was detected in the 8th. week experimental group initially.

2. In Group Ⅱ, hyperkeratosis, squamoid and basaloid epithelial hyperplasia were observed, but dysplasia or papillomatous growth etc. were not seen.

3. In Group Ⅱ, any specific changes were not observed on light-microscope after cessation of chemical treatment, but continuous changes of nuclear, intercellular space and basement membrane were seen on electron-microscope.

4. In Group Ⅲ, hyperkeratosis, squamoid and basaloid epithelial hyperplasia, dysplasia, and papillomatous growth were observed, and carcinoma in situ was also detected in the 9th. week. These changes were much significant than in Group Ⅱ,

but far less than in Group Ⅳ.

5. In Group Ⅳ, dysplasia, carcinoma in situ and invasive carcinoma had been detected two weeks earlier, and basaloid epithelial hyperplasia were markedly presented than in Group Ⅰ.

In this study, the author suggest that Initiation-Promotion Phases were presented on experimental carcinogenesis of buccal mucosa, initiation phase had definite cellular changes, and also these changes were irreversible and had cancer-petentiality.
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