Barker D, Dixon K, Medrano E E, Smalara D, Im S, Mitchell D, Babcock G, Abdel-Malek Z A
Department of Dermatology, University of Cincinnati, Ohio 45267-0592, USA.
Cancer Res. 1995 Sep 15;55(18):4041-6.
Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes contained significantly higher numbers of cyclobutane pyrimidine dimers than did DNA from heavily pigmented melanocytes after irradiation with increasing doses of UVB light. We speculate that the prolonged induction of p53 in lightly pigmented melanocytes arrests them in G1 for a long time period in order to repair extensive DNA damage. The above described differences might partially explain the increased susceptibility of individuals with lightly pigmented skin compared to individuals with dark skin to the photodamaging and photocarcinogenic effects of sun exposure.
黑色素被认为具有光保护作用。为了对此进行研究，我们比较了源自不同色素沉着表型（皮肤类型I - VI）的培养人黑素细胞对不同剂量（11.7至70.1 mJ/cm²）的UVB光单次照射的反应。UVB照射后，色素沉着较重的黑素细胞与色素沉着较轻的黑素细胞相比，存活率相同，但恢复增殖的能力更强。色素沉着较重的黑素细胞中黑色素含量显著增加，而色素沉着较轻的黑素细胞中则未观察到这种情况。无论黑色素含量如何，UVB光照射都会使黑素细胞在G1期停滞，并在4小时内诱导肿瘤抑制蛋白p53的表达。这种诱导在色素沉着较轻的黑素细胞中持续增加直至48小时；然而，在色素沉着较重的黑素细胞中，p53水平在UVB处理后24小时达到峰值，随后下降。此外，随着UVB光照射剂量增加，色素沉着较轻的黑素细胞的DNA中含有比色素沉着较重的黑素细胞的DNA中显著更多数量的环丁烷嘧啶二聚体。我们推测，色素沉着较轻的黑素细胞中p53的长时间诱导使其在G1期长时间停滞，以便修复广泛的DNA损伤。上述差异可能部分解释了与深色皮肤个体相比，浅色皮肤个体对阳光照射的光损伤和光致癌作用更易感性增加的原因。
