Kvam E, Tyrrell R M
Department of Pharmacy and Pharmacology, University of Bath, U.K.
J Invest Dermatol. 1999 Aug;113(2):209-13. doi: 10.1046/j.1523-1747.1999.00653.x.
Highly pigmented, dark skin is more resistant to the harmful effects of solar ultraviolet radiation than light-colored human skin. The extent to which tanning protects skin from harmful effects including induction of skin cancer is not known, however. We have investigated whether the skin pigment, melanin, sensitizes or protects isolated DNA or nuclear DNA in melanoma cells from the induction of the premutagenic oxidative DNA base damage, 8-hydroxy-deoxyguanosine, by ultraviolet A irradiation. Synthetic eumelanin sensitized isolated DNA to induction of the oxidative DNA base damage by ultraviolet A, but it also induced the oxidative DNA base damage in the dark. To study the role of natural melanin in mammalian melanoma cells in the induction of oxidative DNA base damage, melanin synthesis was modulated 5-7-fold in the human melanoma cells GLL19 and IGR1 (which contain both pheomelanin and eumelanin) as well as in the mouse melanoma cells B16 (which contain mainly eumelanin). Increased melanin synthesis clearly did not protect against ultraviolet A-induced oxidative DNA base damage in cells. On the contrary, the human melanoma cells with high melanin content accumulated two times more 8-hydroxy-deoxyguanosine after ultraviolet A irradiation than cells with low melanin content. Furthermore, preirradiation of the human melanoma cells, IGR1, with ultraviolet A 4 h before a second ultraviolet A exposure produced an altered amount of induced 8-hydroxy-deoxyguanosine dependent on the melanin content of the cells. We conclude that stimulation of melanin synthesis, but probably not melanin itself, increases the susceptibility of human melanoma cells to induction of premutagenic oxidative DNA base damage by ultraviolet A irradiation.
色素沉着很深的深色皮肤比浅色人种皮肤对太阳紫外线辐射的有害影响更具抵抗力。然而，晒黑对皮肤免受包括诱发皮肤癌在内的有害影响的保护程度尚不清楚。我们研究了皮肤色素黑色素是否会使黑色素瘤细胞中的分离DNA或核DNA对紫外线A照射诱发的致突变前氧化性DNA碱基损伤（8-羟基脱氧鸟苷）敏感或起到保护作用。合成真黑素使分离的DNA对紫外线A诱发的氧化性DNA碱基损伤敏感，但它在黑暗中也会诱发氧化性DNA碱基损伤。为了研究天然黑色素在哺乳动物黑色素瘤细胞中诱发氧化性DNA碱基损伤的作用，我们在人黑色素瘤细胞GLL19和IGR1（同时含有褐黑素和真黑素）以及小鼠黑色素瘤细胞B16（主要含有真黑素）中，将黑色素合成调节了5至7倍。黑色素合成增加显然不能保护细胞免受紫外线A诱发的氧化性DNA碱基损伤。相反，黑色素含量高的人黑色素瘤细胞在紫外线A照射后积累的8-羟基脱氧鸟苷比黑色素含量低的细胞多两倍。此外，在人黑色素瘤细胞IGR1第二次接受紫外线A照射前4小时先用紫外线A预照射，会产生与细胞黑色素含量相关的诱导型8-羟基脱氧鸟苷量的变化。我们得出结论，黑色素合成的刺激，而非黑色素本身，会增加人黑色素瘤细胞对紫外线A照射诱发的致突变前氧化性DNA碱基损伤的敏感性。
