Rosenstein B S, Phelps R G, Weinstock M A, Bernstein J L, Gordon M L, Rudikoff D, Kantor I, Shelton R, Lebwohl M G
Department of Radiation Oncology, Mount Sinai School of Medicine of NYU, New York 10029, USA.
Photochem Photobiol. 1999 Nov;70(5):798-806.
Sun exposure histories were obtained from a series of patients age 35 or younger following diagnosis and removal of a basal cell carcinoma (BCC). The DNA was extracted from tumor biopsy samples derived from BCC of 10 patients who reported that they did not use sunscreens during youth (age 18 or younger) and 10 patients who routinely employed sunscreens during this age period. Exons 5-9 of the p53 gene were then amplified in three fragments from these samples using a nested polymerase chain reaction (PCR) approach and screened for mutations using an RNA heteroduplex assay. All PCR products displaying evidence of a mutation were sequenced. It was found that 6 of the 10 patients who were not routine sunscreen users displayed mutations in these p53 exons. All of the mutations were located at dipyrimidine sites, five of the six were C-->T transitions and one mutation was a tandem double mutation, consistent with a role for solar UVB in BCC formation. In contrast, only one p53 mutation was detected in the group of 10 patients who routinely employed sunscreens during childhood and adolescence. Hence, a significantly (P = 0.029) lower level of p53 mutations was detected in the BCC obtained from sunscreen users compared with tumors derived from nonusers. These findings suggest that the mechanisms involved in the etiology of skin carcinogenesis differ in sunscreen users compared with people who did not routinely employ sunscreens. These data are also indicative of a protective effect associated with sunscreen use against the formation of p53 mutations. It is possible that the patients who were diagnosed with BCC despite their use of sunscreens possessed a genetic susceptibility for skin cancer formation and developed BCC through a p53-independent pathway. Alternatively, solar UVA wavelengths, that were generally not blocked by the suncare products employed by the sunscreen users, may have played a significant role in BCC development through induction of a mutation(s) in an oncogene and/or a tumor suppressor gene, other than p53, for these patients.
在一系列35岁及以下的患者被诊断并切除基底细胞癌（BCC）后，获取了他们的日晒史。从10名报告在年轻时（18岁及以下）未使用防晒霜的BCC患者以及10名在该年龄段经常使用防晒霜的患者的肿瘤活检样本中提取DNA。然后使用巢式聚合酶链反应（PCR）方法从这些样本中扩增p53基因的外显子5 - 9，分为三个片段，并使用RNA异源双链分析筛选突变。对所有显示有突变迹象的PCR产物进行测序。结果发现，10名不经常使用防晒霜的患者中有6名在这些p53外显子中出现了突变。所有突变都位于二嘧啶位点，6个突变中有5个是C→T转换，1个突变是串联双突变，这与太阳UVB在BCC形成中的作用一致。相比之下，在10名在儿童期和青春期经常使用防晒霜的患者组中仅检测到1个p53突变。因此，与未使用者的肿瘤相比，在使用防晒霜者的BCC中检测到的p53突变水平显著降低（P = 0.029）。这些发现表明，与未经常使用防晒霜的人相比，使用防晒霜者皮肤癌发生病因的机制有所不同。这些数据也表明使用防晒霜对p53突变的形成具有保护作用。尽管使用了防晒霜但仍被诊断为BCC的患者可能具有皮肤癌形成的遗传易感性，并通过p53非依赖途径发展为BCC。或者，防晒霜使用者使用的防晒产品通常不能阻挡的太阳UVA波长，可能通过诱导除p53之外的癌基因和/或肿瘤抑制基因突变，在这些患者的BCC发展中起了重要作用。
