Sondergaard J, Lerche A, Bohr V, Leik V, Wadskov S
Acta Derm Venereol Suppl (Stockh). 1979;87:59-63.
An electron microscopic technique has been used to visualize crosslinks after total denaturation on DNA isolated from epidermis and dermis in patients with psoriasis treated with 8-methoxypsoralen (8-MOP) and irradiation with ultraviolet light at 360 nm (PUVA treatment). This technique facilitated accurate measurements of the number and density of DNA interstrand crosslinks. 30 biopsies from 14 patients were studied and a total of 9503 DNA molecules were scored in the electron-microscope, 6 patients were treated topically with 8-MOP and 10 were on systemic treatment. Two of the patients on topical treatment had previously been on systemic treatment. 1% of all DNA molecules contained 3 or more cross-links. The overall frequency of cross-links was almost identical in the epidermis (1.1%) and in the dermis (0.9%) and, furthermore, virtually the same in patients on topical and systemic PUVA treatment. The total number of crosslinks was of the same magnitude as that previously found in normal human skin. (V. Bohr et al., Acta Dermatovener, in press.) No significantly increased damage of the genetic material (DNA) was demonstrated in our study as a consequence of the PUVA treatment using 8-MOP. We have previously shown (V. Bohr & A. Lerche, Biochim Biophys Acta, in press) that 8-MOP induced crosslinks after irradiation at 360 nm in an in vitro system of pure DNA. In this system a correlation was established between the density of crosslinks formed and irradiation time, concentration of 8-MOP, and irradiation intensity.
一种电子显微镜技术已被用于观察用8-甲氧基补骨脂素(8-MOP)治疗并经360nm紫外线照射(光化学疗法治疗)的银屑病患者表皮和真皮中分离出的DNA完全变性后的交联情况。该技术有助于准确测量DNA链间交联的数量和密度。对14名患者的30份活检样本进行了研究,在电子显微镜下共对9503个DNA分子进行了评分,其中6名患者接受了8-MOP局部治疗,10名患者接受了全身治疗。两名接受局部治疗的患者之前曾接受过全身治疗。所有DNA分子中有1%含有3个或更多交联。表皮(1.1%)和真皮(0.9%)中的交联总频率几乎相同,此外,接受局部和全身光化学疗法治疗的患者中交联频率实际上也相同。交联的总数与之前在正常人类皮肤中发现的数量相当。(V. 玻尔等人,《皮肤病学与性病学学报》,即将发表。)在我们的研究中,未证明使用8-MOP进行光化学疗法治疗会导致遗传物质(DNA)受到显著增加的损伤。我们之前已经表明(V. 玻尔和A. 勒彻,《生物化学与生物物理学报》,即将发表),在纯DNA的体外系统中,8-MOP在360nm照射后会诱导交联。在这个系统中,形成的交联密度与照射时间、8-MOP浓度和照射强度之间建立了相关性。