Indomethacin이 Hamster 협낭의 DMBA 유도 상피암 발암과정에서 Langerhans 세포와 Prostaglandins에 미치는 영향에 관한 연구

The effect of indomethacin on langerhans cells and prostaglandins in DMBA induced carcinogenesis of buccal pouch in hamster

This study was undertaken to investigate the effect of indomethacin on Langerhans cells and prostaglandins in 9,10-dimethyl-1,2-benzanthracene (DMBA) induced carcinogenesis of hamster buccal pouch. In this study, sixty hamsters-about 120 gram of body weight-were used classifying as 1) six hamsters of normal group received no treatment, 2) six hamsters of control group treated with heavy mineral oil 3 times a week, 3) twenty four hamsters of experimental group Ⅰ treated with 0.5% DMBA in heavy mineral oil 3 times a week and administered 20 ㎍/㎖ indomethacin in drinking water ad lib, 4) twenty four hamsters of experimental group Ⅱ treated with 0.5% DMBA in heavy mineral oil 3 times a week. The animals of normal and control groups were sacrificed 5th and 18th week, while those of experimental group Ⅰ and Ⅱ were sacrificed 5th, 7th, 9th, 11th, 13th, 15th, 17th and 18th week after experiment. The buccal pouches were excised. The tissues for hematoxylin-eosin stain and peroxidase antiperoxidase stain were fixed in 10% formalin and processed in a routine manner, and the tissues for thin layer chromatography were kept frozen -70℃. Densitometer scan and Packard-tri-carb counter were utilized for the thin layer chromatography of arachidonic acid metabolites. Following results were obtained. 1) In general, the mucosal changes of hamsters in experimental groupⅠ appeared 1 ~ 2 weeks earlier than those in experimental group Ⅱ during the early 10 weeks, but intra-oral changes after 10 weeks showed more distinct in experimental group Ⅰ. 2) The histologic findings of control tissues represented sinular to those of normal group. The tissues of experimental groups showed hyperkeratosis at 5th week, acanthosis at 7th week, dysplasia at 11th week, and squamous cell carcinoma at 13th week. There were no significent differences in microscopic findings between experimental group Ⅰ and Ⅱ. 3) Langerhans cell was not observed within epidermis of all groups, however, PAP positive cells were observed within submucosal area. In experimental group, PAP positive cells of submucosal area were increased from 5th week and decreased from 11 th week respectively. At 13th week, cancerous area had fewer PAP positive cells than in contral group and at 18th week, the PAP positive cells in non-cancerous area showed approximately the same number as control group. 4) The arachidonic acid metabolites synthesized in entire tissue homogenates included prostaglandin D₂, prostaglandin E₂, prostaglandin F₂α in that order of relative abundances, but not included 6-keto-prostaglandin F₁α and thromboxane B₂. 5) The relative abundances of arachidonic acid metabolites in experimental groupⅠ were a slight decrease in prostaglandin D₂ and a slight increase in prostaglandin E₂, however, there was little variation in prostaglandin F₂α during experiment. 6) The relative abundances of arachidonic acid metabolites in experimental group Ⅱ were a significant decrease in prostaglandin D₂ and a significant increase in prostaglandin E₂, however, there was little variation in prostaglandin F₂α during experiment. 7) In ratios of prostaglandins in experimental and control groups, there were a slight variation in prostaglandin D₂ and prostaglandin F₂α but a significant increase in prostaglandin E₂. 8) The ratios of prostaglandin D₂ in experimental group Ⅰ and Ⅱ compared to control group were slight differences. The ratio of prostaglandin E₂ in experimental group Ⅰ was increased up to the 15th week, while in experimental group Ⅱ showed continuous increase. The ratio of prostaglandin F₂α showed slight differences after 17th week.