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C57 BL Mice에서의 Psoralen 유도체를 이용한 국소 광화학요법 후 표피내 멜라닌세포 변화에 관한 비교연구

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 (The) study on the effects of psoralen derivatives on epidermal melanocytes in C57 BL Mice after topical photochemotherapy 
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[한글] 백반증은 저색소성 피부질환중 대표적인 것으로 전 인구의 약 1% 정도에서 발병하는 비교적 흔한 질환으로 장기간의 치료를 요하는 난치성 질병이다. 1948년 El-Mofty에 의해 광화학요법이 처음 도입된 이래로 30여년이 지난 후 광독성약물인 psoralen과 UVA를 이용하는 광화학요법(PUVA)이 개발되어 사용되어지고 있다. 광독성 약물에는 DNA와 작용하여 biadducts를 형성하는 bifunctional psoralen과 monoadducts 를 형성하는 monofunctional psoralen으로 나눌수 있는데 최근에 들어 광독성이 거의 없다고 알려진 monofunctional psoralen에 관심이 쏠리고있다. 1940년대와 50년대에 협심증의 치료제로 쓰여졌던 khellin이 8-methokypsoralen과 비슷한 구조를 가지고 있다는 점에 착안하여 백반증의 치료에 쓰여졌고 황독성이 적은 광활성물질인 각구조 furocoumarin (angular furocoumarin)에 속하는angelicin이 건선에 쓰여진 예가 있었다. 저자는 광독성반응이 적다고 알려진 물질인 angelicin과 khellin을 사용하여 국소 황화학요법시 색소침착 효과를 알아보고자 하였다. 실험동물로는 성숙된 웅성 C57 BL mice 93마리를 대상으로 UVA 단독조사군과 광화학요법군으로 나누고 다시 광화학요 법군을 trimethylpsoralen(TMP), khellin, angelicin군으로 나누었으며 이들 각각에 대해 0.02%, 0.1%, 0.5%농도로 C57 BL mice 귀의 배부에 각 약물을 0.1ml씩 도포하였다. 광화학요법은 1주에 3회씩 5주간 실시하였으며 자외선A는 약물도포 30분후에 조사하여 다음과 같은 결과를 얻었다. 1) 광화학요법군이 UVA단독 조사군보다 멜라닌세포 수의 현저한 증가를 보였다. 모든 광화학요법군에서 자외선 조사횟수의 증가에 따라 멜라닌세포 수가 증가하였으며 모든군에서 3주와 5주에 유의한 증가를 보였다. 같은 자외선 조사횟수와 같온 농도하에서는 TMP 도포군이 가장 뚜렷한 멜라닌세포 수의 증가를 보였고 khellin 도포군, angelicin 도포군의 순으로 증가를 보였다. 2) TMP도포 후 자외선 조사군에서는 자외선 조사횟수의 증가에 따라 대체적으로 멜라닌세포 면적의 증가를 보였으나 angelicin과 khellin군에서는 뚜렷한 면적의 증가를 보이지 않았다. 3) TMP도포 후 자외선 조사군에서는 자외선 조사횟수의 증가에 따라 대체적으로 멜라닌세포 둘레의 증가를 보였으나 angelicin과 khellin군에서는 뚜렷한 둘fp길이의 증가를 보이지 않았다. 이상의 결과로 국소 광화학요법시 같은농도와 같은 자외선 용량에서 TMP, khellin, angelicin순으로 색소침착 효과가 있음을 알 수 있었다.
[영문] Vitiligo is an chronic progressive, common skin disorder of unknown etiology, which affects 1% of normal population, and needs long-term treatment. Photochemotherapy was introduced into modem dermatology by El-Mofty in 1948 and it took another 30 years before photochemotherapy with oral psoralen and UVA was used in the treatment of vitiligo and psoriasis. Psoralens are divided into bifunctional ones and monofunctional ones. Monofunctional psoralen plus UVA radiation are not severly phototoxic and have less mutagenic activity than the bifunctional p soralens plus UVA radiation. For these reasons, they have received considerable attention in recent years as potential alternative therapeutic agents for vitiligo and psoriasis. Khellin has been widely used in the 1940s and 1950s for long term treatment of angina pectoris and has some structural similarities to 8-methoxypsoralen. Angular furocoumarins like angelicin are being tested for their clinical effectiveness in order to find the compound with the least risk of side effects. Encouraging experimental results in the treatment of psoriasis have been reported. The purpose of this study is to compare the pigment producing effect of monofunctional psoralens as khellin and angelicin with trimethylpsoralen(raP).Ninty three C57 black mice were divided into UVA radiation alone and photochemotherapy groups. Photochemotherapy group was subdivided into TMP, khellin, angelicin applied group and each group was subdivided 0.02%, 0.1%, 0.5% by its concentration. This psoralens are applied to dorsum of ears of mice at the dose of 0.1ml. Photochemotherapy was performed three times a week for five weeks. The results are summerized as follows 1) In the Photochemotherapy group , there was a marked increase in the number of melanocytes compared with the UVA alone group. There was positive correlation between number of melanocytes and frequency of UVA irradiation. The comparison of melanocyte numbers between different psoralens after five weeks of photochemotherapy showed a significant difference in decreasing order at TMP, khellin, angelicin. 2) The area of the melanocytes was larger in the TMP group after five weeks of photochemotherapy than other group. The area of melanocytes in khellin and angelicin groups were not increased by increasing the frequency of the UVA irradiation. 3) The perimeter of melanocytes was the largest in the TMP group at all concentrations after three and five weeks of photochemotherapy. The perimeter of melanocytes in khellin and angelicin groups were not increased by increasing frequency of the UVA irradiation. The numbers, areas and perimeters of the melanocytes after topical photochemotherapy were increased more in the TMP group compared to khellin and angelicin. Because monofunctional psoralens like angelicin and khellin, plus UVA radiation are not severely phototoxic, it would be worthwhile studying khellin and angelicin photochemotherapy for its possible efficacy in vitiligo with studying relation between topical concentration and Phototoxicity.
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