백서 구개점막의 4-Nitroquinoline-N-Oxide(4 NQO)- 유도 상피암의 二相발암과정에 관한 조직병리학적 연구

THE HISTOPATHOLOGICAL STUDY ON TWO-PHASE CARCINOGENESIS OF 4-NITROQUINOLINE-N-OXIDE(4NQO)-INDUCED ORAL CARCINOMA IN PALATAL MUCOSA OF WHITE RAT

Studies related to two-phase mechanism of oral carcinogenesis have never been carried out in palatal mucosa. This report was undertaken to study the histopathological and ultrastructural changes during two-phase carcinogenesis of 4-Nitroquinoline-N-Oxide (4NQO)-induced oral carcinoma on the mucosa of palate of white rat. The purpose of this study were to prove two-phase carcinogenesis on palatal mucosa, and to investigate histological changes on initiation and promotion process of palatal cancer by chemical carcinogenesis. For this study, the author used Sprague-Dawley white rats for experimental animals and used 4-NQO in propane-1,2-diol. The experimental animals were divided into two control groups and five experimental groups, and experimental materials for carcinogenesis were applied on palatal mucosa of white rats three times weekly as follows. Control Group A(33): Painting with 0.5% 4-NQO for 32 weeks. Control Group B(33): Painting with propane-1,2-diol for 32 weeks. Experimental Group Ⅰ(33): Painting with 0.1% 4NQO for 10 weeks, no treatment for following 6 weeks, and followed by 0.5% 4NQO for 18 weeks. Experimental Group Ⅱ(33): Painting with 0.1% 4NQO for 10 weeks, no-treatment for following 6 weeks, and followed by 0.1% 4NQO for 18 weeks. Experimental Group Ⅲ(33): Painting 0.1% 4NQO for 10 weeks, no-treatment for following 6 weeks, and followed by propane-1,2-diol for 18 weeks. Experimental Goup Ⅳ(33): Painting with propane-1,2-diol for 10 weeks, no-treatment for following 6 weeks, and followed by 0.5% 4NQO for 18 weeks. Experimental Group Ⅴ(33): Painting with propane-1,2-diol for 10 weeks, no-treatment for following 6 weeks, and followed by 0.1% 4NQO for 18 weeks. The animals were sacrificed every other week serially, and chemical-treated palatal mucosa were excised and examined grossly, light-microscopically and electron-microscopically. The obtained results were as follows.: 1. In Control Group A, hyperkeratosis, acanthosis, dyskeratosis, epithelial dysplasia, and invasive carcinoma were all seen on light-microscope. Invasive carcinoma was noticed at first in 14th. week experimental group, but the most of invasive carcinomas were detected after 25th. week. In control Group B, there was no specific difference than normal tissue histopathologically except slight hyperkeratosis in 20th. week experimental group. 2. The promotion effect on palatal mucosa by 0.1% and 0.5% 4NQO (promotors) might not be influenced by drug toxicity, and palatal mucosa also might not be influenced from carcinogen as much as tissue destruction due to drugs. 3. In Experimental Group Ⅰ & Ⅱ, acanthosis on light-microscope and nuclear changes, widening of intercellular space and irregularities of basal layers on electron-microscope were being found and more changed after finishing of initiation by 0.1% 4NQO. This may be demonstrated the irreversible process for tumor-stem cells of palatal mucosa by 0.1 % 4NQO-initiation. 4. In this study, the promotion phase toward true neoplasms did not observed in topical application of 0.1%, 0.5% 4-NQO and propane-1,2-diol on palatal mucosa of white rats which were initiated by 0.1% 4-NQO.