Indomethacin이 4-Nitroquinoline-N-Oxide(4-NQO) 유도 백서 구개암 발암과정에서 prostaglandins에 미치는 영향에 관한 연구

Abstract

[한글]

본 실험은 indomethacin이 4 NQO유도 백서구개암의 발암과정에서 prostaglandins에 미치는 효과를 연구하기 위하여 시행되었다.

본 실험에서는 체중 100g내외의 Sprague-Dawley계 웅성백서 128마리를 정상군 16마리, 대조군 16마리, 실험 Ⅰ군과 Ⅱ군 각 48마리씩으로 나누어, 정상군은 고형시판사료와 수도물로써 사육하고, 대조군은 희석용매인 prophylene을 주 3회씩 면봉으로 구개부에 도포

하였으며, 실험 Ⅰ군은 prophylene에 녹인 0.5% 4-NQO용액을 주3회 구개부에 도포하였으며, 실험Ⅱ군은 prophylene에 녹인 0.5% 4-NQO 용액을 같은 방법으로 도포하면서 20μg/㎖의 indomethacin을 녹인 식수를 공급하였다.

정상군과 대조군은 실험 7, 13, 19, 25주째에 각 4마리씩, 실험 Ⅰ, Ⅱ군은 실험 7주째부터 29주째까지 격주로 4마리씩 회생시켜, 즉시 구개부와 설부를 적출하여 deep freezer에서 -70℃로 보관하였다.

Arachidonic arid대사산물을 측정하기 위한 thin layer chromatography를 위하여 조직을 생화학적 처리한 다음, densitometer scan과 beta-counter counting을 시행하여 아래와 같은 결론을 얻었다.

1. 정상군과 대조군은 실험기간에 따른 arachidonic acid 대사산물의 양적변화가 거의 없었으며, 공히 prostaglandin D^^2, 6-keto-prostaglandin F^^1α, prostaglandin E^^2, thromboxane B^^2, prostaglandin F^^2α의 순으로 나타났다.

2. 실험 Ⅰ군에서의 prostaglandin D^^2와 prostaeandin E^^2는 증가되었고 prostaglandin F^^2α는 별 변화가 없었으며,6-keto-prostaglandin F^^1α와 thromhoxane B^^2는 감소되었다.

3. 실험 Ⅱ군에서도, prostaglandin D^^2와 prostaglandin E^^2는 증가되었고, prostaglandin F^^2α는 별 변화가 없었으며, 6-keto- prostaglandin F^^1α와 thromboxane B^^2 는 감소되었다.

4. prostaglandin D^^7와 prostaglandin E^^2의 증가폭과 6-keto-prostaglandin F^^2α와 thromboxane B^^2의 감소폭은 실험Ⅱ군에 비해 실험 Ⅰ군에서 더 컸으며, pmstaglandin F^^2α,는 실험군, 정상군, 대조군 공히 별 변화가 없었다.

5. 실험 Ⅰ, Ⅱ군의 구개부에서의 prostaglandin D^^2와 prostaglandin E^^4의 증가폭과 6-keto-prostaglandin F^^1α와 thromboxane B^^2의 감소폭이 설부에 비해 더 컸다.

[영문]

This study was undertaken to investigate the effect of indomethacin on prostaglandins in 4-Nitroquinoline-N-Oxide (4-NQO) induced palatal carcinoma of albino rats.128 Sprague-Dawley strain albino rata- about 100g in body weight - were used in this study, divided into as belows;

1. Normal group (16-albino rats) with no treatment,

2. Control group (16-albino rats) treated with prophylene application onto palatal mucosa 3 times a week.

3. Experimental group Ⅰ (48-albino rats) treated with 0.5% 4-NQO in prophylene application onto palatal mucosa 3 times a week.

4. Experimental group Ⅱ (48-albino rats) treated with 0.5% 4-NQO in prophylene application with administered 20μg/㎖ of indomethacin in drinking water ad. lib. Four animals were sacrificed 7th, 13th, 19th and 25th week respectively in normal

and control group, and 7th, 9th, 11th, 13th, 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th week respectively in experimental group Ⅰ and Ⅱ at each time.

The palatal and lingual tissues were excised and kept frozen at -7O℃.

Densitometer scan and Beta-counting counter were used far the thin layer chromatography of the arachidonic acid metabolites.

The obtained results were as belows;

1. In normal and control group, there was little change of the arachidonic acid metabolites during experiment period, and the tissue homogenates included prostaglandin D^^2, 6-keto-prostaglandin F^^1α, prostaglandin E^^2, thromboxane B^^2, prostaglandin F^^2α in that order of relative abundances.

2. In experimental group Ⅰ, prostaglandin D^^2 and prostaglandin E^^2 were increased, while 6-keto-prostaflandin F^^1α and thromhoxane B^^2 were decreased in relative abundances of arachidonic acid metabolites. And there was little chance in

prostaglandin F^^1α.

3. In experimental group Ⅱ, prostaglandin D^^2 and prostaglandin E^^2 were increased, while 6-keto-prostaglandin F^^lα and thromboxane B^^2 were decreased in relative abundances of araohidonic acid metabolites. And there was little change in

prostaglandin F^^2α also.

4. In the range of increase in prostaglandin D^^2 and prostaglarldin E^^2, and that of decrease in 6-keto-prostaglandin F^^lα and thromboxane B^^2 in relative abundances, there was wider in experimental group Ⅰ than in group Ⅱ.

5. In the range of increase in prostaglandin D^^2 and prostaglandin E^^2, and that of decrease in 6-keto-prostaglandin F^^1α and thromboxane B^^2 in relative abundances, there was wider in palatal mucosa than in lingual mucosa in experimental group Ⅰ and Ⅱ.