Böni R, Matt D, Burg G, Tronnier M, Vortmeyer A, Zhuang Z
Department of Dermatology, University Hospital, Zurich, Switzerland.
Arch Dermatol. 1998 Jul;134(7):853-6. doi: 10.1001/archderm.134.7.853.
Transformed melanocytes in atypical nevi, which are thought to be precursors of melanoma, are frequently deleted on chromosomes 1p, 9q, and 9p21 (p16 locus). Single UV irradiation induces histological changes that are similar to those of atypical nevi and, in part, of melanoma in situ.
To determine the effects of UV irradiation on benign melanocytic nevi in vivo.
We investigated one half of a symmetric nevus 1 week after a single UV exposure with 4 times the patient's minimal erythema dose and compared it with the nonirradiated, shielded half of the same nevus. Two to 3 areas containing 5 to 30 melanocytes in 7 nevi were microdissected (a total of 18 areas in each nonirradiated and irradiated part), followed by a single-step DNA extraction. Extracted genomic DNA was amplified using a polymerase chain reaction with polymorphic markers D1S450 (1p), D9S12 (9q), IFNA, and D9S171 (9p21) and subjected to autoradiography.
Two, 3, 2, and 2 of 18 areas were homozygous for D1S450, D9S12, IFNA, and D9S171, respectively. No allelic loss could be demonstrated in either nonirradiated or irradiated nevi.
Acute histological changes demonstrated in melanocytic nevi after UV irradiation are not followed by allelic loss on identical chromosomal areas found in dysplastic melanocytes of atypical nevi. This finding supports the hypothesis that initial nonspecific genetic events may occur after UV irradiation, followed by an increase in various repair mechanisms potentially leading to specific genetic damage and loss of heterozygosity; however, loss of heterozygosity is not detectable at an early stage.
非典型痣中的转化黑素细胞被认为是黑色素瘤的前体,其在染色体1p、9q和9p21(p16位点)上经常发生缺失。单次紫外线照射可诱导组织学变化,这些变化与非典型痣以及部分原位黑色素瘤的变化相似。
确定紫外线照射对体内良性黑素细胞痣的影响。
我们在单次紫外线暴露1周后,用患者最小红斑量的4倍剂量照射对称痣的一半,并将其与同一痣未照射、受保护的另一半进行比较。在7个痣中,对2至3个含有5至30个黑素细胞的区域进行显微切割(未照射和照射部分各18个区域),然后进行单步DNA提取。使用聚合酶链反应和多态性标记D1S450(1p)、D9S12(9q)、IFNA和D9S171(9p21)对提取的基因组DNA进行扩增,并进行放射自显影。
18个区域中,分别有2个、3个、2个和2个区域的D1S450、D9S12、IFNA和D9S171为纯合子。在未照射或照射的痣中均未发现等位基因缺失。
紫外线照射后黑素细胞痣中出现的急性组织学变化,并未伴随非典型痣发育异常黑素细胞中相同染色体区域的等位基因缺失。这一发现支持了以下假设:紫外线照射后可能会发生初始的非特异性基因事件,随后各种修复机制增加,可能导致特异性基因损伤和杂合性缺失;然而,在早期阶段无法检测到杂合性缺失。