수종의 광독성 약물 도포의 자외선조사가 멜라닌색소에 미치는 영향 연구

Abstract

[영문]

[한글]

백반증의 치료로서 병소의 크기가 작을 때나 환자의 연령이 낮을 때 국소광화학요법이

널리 사용되나 색소 침착에 필요한 최저 광독량을 유발하는 자외선 노출시간의 조절이 매

우 힘들어서 치료도중 홍반이나 수포형성이 일어날 수 있으므로 부작용이 적고 효과가 좋

은 약제의 선택과 적절한 농도의 선정이 중요하다.

8-Methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 및 4,5, 8,-trimethylpsorale

n (TMP)은 광화학요법시 사용되는 광독성 약물들로서 이들간의 색소침착효과에 대한 비교

연구는 드물다.

본 연구에서는 성숙된 수컷 흑색쥐 (C 57 BL mouse) 116마리를 대상으로8-MOP, 5-MOP,

TMP 각각에 대해 농도0.02%, 0.1%, 0.5%를 도포한 9군과 기저용액만을 도포한 대조군으로

나누고 약물 도포 3O분후에 UVA를 1주에 2회씩 7주간 조사하였다. UVA조사량은 첫주는1

회 150mJ/cm**2이며, 둘째주는 200mJ/cm**2, 셋째주는 250mJ/cm**2, 넷째주 이상은 300mJ

/cm**2이었다. UVA조사후 1주, 3주, 5주, 7주에 피부조직을 생검하여 Split-Dopa 염색을

시행한 후 색소세포의 변화를 관찰하기 위하여 색소세포의수, 면적, 둘레 길이를 측정하

여 다음과 같은 결과를 얻었다.

Studies on the effects of UV irradiation on melanocytes after application of

various phototoxic drugs

You Chan Kim

Deparenent of Medical Science The Graduate School, Yonsei University

(Directed by Professor Yoon-Kee Park, M.D.)

For treatment of vitiligo in patients of young age or with small areas of

involvements topical photochemotherapy is widely used. However, it is very

difficult to control the amount of time of ultraviolet exposure for induction of

the minimum phototoxicity necessary for pigment deposition. Therefore, during

ireatrnent of vitiligo, erythema or vesicle formation can occur, which necessitates

the selection of drugs with few complications and good effect as well as the proper

concentration.

8-Methoxypsoralen(8-MOP), 5-methoxypsoralen(5-MOP) and 4, 5, 8-trimethylpsoralen

(TMP) are the phototoxic drugs used in photochemotherapeutic treatment and

comparative studies between these three drugs for pigment deposition have been

rarely made.

In this study,116 mature black male mice of C-57 BL strain were divided into 9

test groups and 1 control group, the former were painted with 8-MOP, 5-MOP and TMP

in concentrations of 0.02%, 0.1% and 0.5% each and the latter with a basic

solution, and UVA was irradiated after 30 minutes. The amounts of UVA exposure were

150mj/cm**2 in the first week, and 200mj/cm**2 in the second week, 250mj/cm**2 in

the third week and 300mj/cm**2 from the fourth week on twice weekly for 7 weeks.

Skin biopsies were performed at 1, 3, 5 and 7 weeks after UVA irradiation and

were stained with split-dopa and the number, area and perimeter of the melanocytes

were measured to observe the changes of the cells. The following results were

obtained:

1. Comparison of the number of melanocytes

After 3 weeks of drug painting, significantly more melanocytes were seen in the

THP-painted group than in 5-MOP- and 8-MOP-painted groups(P<0.05). Between the

8-MOP-and 5-MOP-painted groups, the only difference was the appearance of

significantly more melanocytes in the 0.l% and 0.5% 5-MOP-painted groups after 5

weeks of painting and also more cells in the 0.l% 8-MOP-painted group after 7

weeks(P<0.05).

In a comparative study between the phototoxic drugs at 0.l% concentration, the

changes was 5, 7, 3, 1 week in a decreasing order and the comparison between the

concentrations after 5 weeks of painting showed changes in a decreasing order of

0.1%, 0.5%, 0.02%.

2. Comparison between the areas of melanocytes

The area of the melanocyte was larger in the TMP-painted group than others at a

concentiation of 0.5% after 1 and 3 weeks of painting, and at 0.l% and 0.5% after 5

weeks, and at all concentrations after 7 weeks (P<0.05). Between the 8-MOP-painted

group and 5-MOP-painted group, there were no differences except there were

significantly larger melanocytes in 8-MOP-painted group after 1 week of painting,

and in the 0.1% 8-MOP-painted group after 7 weeks and larger cells were observed in

0.1% 5-MOP-painted-group after 5 weeks (P<0.05).

In a comparative study between the phototoxic drugs at 0.1% concentration, the

changes was 5, 3, 7, 1 week in a decreasing order and the comparison between the

concentrations after 5 weeks of painting showed changes in a decreasing order of

O.1%, 0.5%, 0.02%.

3. Comparison between the perimeter of melanocytes

The perimeter of melanocytes was longer in the TMP-painted group than others at

all the concentrations after 3 weeks of painting and in the 0.02% and 0.5% groups

after 5 weeks (P<0.05). However, an unexpectedly lower value was obtained in the

0.1% group after 1 week of painting (P<0.05), There were no differences between

8-MOP-painted group and 5-MOP-painted group except that the perimeter of

melanocytes was significantly longer in the 0.5% 8-MOP-painted group after 1 week

of painting and in the 0.1% and 0.5% groups after 7 weeks and was longer in the

0.l% 5-MOP-painted-group after 5 weeks(P<0.05).

In a comparative study between the phototoxic drugs at 0.1% concentration, the

changes was 5,3,7,1 week in decreasing order and the comparison between the

concentrations after 5 weeks of painting showed changes in a decreasing order of

0.1%, 0.5%, 0.02%.

The results of measuring the number, area, and perimeter of the melanocytes after

painting and ultraviolet radiation were higher in the TMP-painted group than in the

8-MOP or 5-MOP painted groups, and there were no differences between the 8-MOP and

5-MOP painted groups. The weekly changes showed an increasing value until 5 weeks,

and after that showed a decrease. In comparison of the drug concentrations

used,0.1% produced the same or higher values than 0.5%.

Few studies have been done on 5-MOP in photochemotherapy, but in this study, it

produced a similar pigment-producing effect as 8-MOP. Therefore, we think that it

is a drug worth studying to a greater degree in the future.