A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage.
A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage.
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DOI：
10.1158/1940-6207.capr-21-0399
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
Grossman D
中科院分区：
文献类型：
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作者：
Okwundu N;Rahman H;Liu T;Florell SR;Boucher KM;Grossman D
DNA损伤在紫外线（UV）诱导的黑色素瘤中发挥着作用。我们先前表明，阿司匹林（阿萨）可以抑制前列腺素E2（PGE 2），并保护黑素细胞免受紫外线诱导的DNA损伤，并建议在急性阳光照射前服用阿萨可以降低黑色素瘤的风险。我们进行了一项前瞻性随机安慰剂对照试验，以确定口服阿萨是否可以抑制血浆和痣中的PGE 2，并保护痣免受紫外线诱导的DNA损伤。在获得95名黑色素瘤风险增加的受试者的血浆并确定最小平均剂量（MED）后，他们被随机分配接受每日剂量的安慰剂、81 mg阿萨或325 mg阿萨，以双盲方式持续1个月。在此干预后，使用太阳模拟器照射一个痣（剂量= 1或2 MED）。一天后，重新测定MED，获得第二份血浆样本，并去除UV照射的痣和未照射的痣。在阿萨组受试者的第二份血浆样本中检测到阿萨代谢物。接受阿萨和安慰剂的患者在干预前后MED无显著差异。与安慰剂相比，在接受阿萨的受试者中，在血浆（第二次与第一次样本）和痣（未照射和UV治疗）中检测到PGE 2水平显著降低。然而，比较阿萨组和安慰剂组的UV治疗痣，并没有发现CD 3细胞浸润或8-氧代鸟嘌呤和环丁烷嘧啶二聚体的显着减少。因此，阿萨不能有效地保护痣免受太阳模拟紫外线诱导的炎症和DNA损伤的条件下检查。尽管有希望的理由，阿萨在常规剂量不能保护痣对紫外线诱导的DNA损伤的条件下检查。
DNA damage plays a role in ultraviolet (UV)-induced melanoma. We previously showed that aspirin (ASA) can suppress prostaglandin-E2 (PGE2) and protect melanocytes from UV-induced DNA damage in mice, and suggested that taking ASA before acute sun exposure may reduce melanoma risk. We conducted a prospective randomized placebo-controlled trial to determine if orally administered ASA could suppress PGE2 in plasma and nevi and protect nevi from UV-induced DNA damage. After obtaining plasma and determining the minimal erythemal dose (MED) in 95 subjects at increased risk for melanoma, they were randomized to receive a daily dose of placebo, 81 mg ASA, or 325 mg ASA, in double-blind fashion for one month. After this intervention, one nevus was irradiated (dose = 1 or 2 MED) using a solar simulator. One day later, MED was re-determined, a second plasma sample was obtained, and the UV-irradiated nevus and an unirradiated nevus were removed. ASA metabolites were detected in the second plasma sample in subjects in the ASA arms. There were no significant differences in the pre- and post-intervention MED between those patients receiving ASA and placebo. Significantly reduced PGE2 levels were detected in plasma (second vs. first samples) and in nevi (both unirradiated and UV-treated) in subjects receiving ASA compared to placebo. Comparing UV-treated nevi from the ASA and placebo cohorts, however, did not reveal significant reductions in CD3-cell infiltration or 8-oxoguanine and cyclobutane pyrimidine dimers. Thus ASA did not effectively protect nevi from solar-simulated UV -induced inflammation and DNA damage under the conditions examined. Despite promising rationale, ASA at conventional dosing was not able to protect nevi against UV-induced DNA damage under the conditions examined.