Hennessey Rebecca C, Holderbaum Andrea M, Bonilla Anamaria, Delaney Conor, Gillahan James E, Tober Kathleen L, Oberyszyn Tatiana M, Zippin Jonathan H, Burd Christin E
Department of Cancer Biology and Genetics, Biomedical Research Tower, The Ohio State University, Columbus, OH, USA.
Department of Molecular Genetics, Biomedical Research Tower, The Ohio State University, Columbus, OH, USA.
Pigment Cell Melanoma Res. 2017 Sep;30(5):477-487. doi: 10.1111/pcmr.12601. Epub 2017 Jul 4.
To mitigate melanoma risk, sunscreen use is widely advocated; yet, the ability of sunscreens to prevent melanoma remains controversial. Here, we test the tenet that sunscreens limit melanoma risk by blocking ultraviolet radiation (UV)-induced DNA damage using murine models that recapitulate the genetics and spontaneous evolution of human melanoma. We find that a single, non-erythematous dose of UV dramatically accelerates melanoma onset and increases tumor multiplicity in mice carrying an endogenous, melanocyte-specific NRas allele. By contrast, transient UV exposure does not alter tumor onset in mice lacking p16 or harboring an NRas allele. To block the rapid onset of melanoma cooperatively caused by UV and NRas , we employed a variety of aerosol sunscreens. While all sunscreens delayed melanoma formation and blocked UV-induced DNA damage, differences in aerosol output (i.e., amount applied/cm ) caused variability in the cancer preventative efficacy of products with identical sunburn protection factor (SPF) ratings.
为降低黑色素瘤风险，广泛提倡使用防晒霜；然而，防晒霜预防黑色素瘤的能力仍存在争议。在此，我们使用模拟人类黑色素瘤遗传学和自然演变的小鼠模型，来检验防晒霜通过阻断紫外线（UV）诱导的DNA损伤从而限制黑色素瘤风险这一原则。我们发现，单次非红斑剂量的紫外线会显著加速携带内源性黑素细胞特异性NRAS等位基因的小鼠的黑色素瘤发病，并增加肿瘤多样性。相比之下，短暂紫外线照射不会改变缺乏p16或携带NRAS等位基因的小鼠的肿瘤发病情况。为协同阻断由紫外线和NRAS共同导致的黑色素瘤快速发病，我们使用了多种气溶胶防晒霜。虽然所有防晒霜都延迟了黑色素瘤的形成并阻断了紫外线诱导的DNA损伤，但气溶胶输出量（即每平方厘米涂抹量）的差异导致具有相同防晒系数（SPF）等级的产品在癌症预防效果上存在差异。
