INDUCTION OF MELANOMA WITH UV-A

UV-A 诱导黑色素瘤

• 批准号: 2394326
• 负责人: RONALD D LEY
• 金额: $ 7.33万
• 依托单位: LOVELACE RESPIRATORY RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-02 至 1997-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2394326
• 关键词: DNA methylation; benzanthracenes; carcinogen testing; gene mutation; melanocyte; melanoma; mutagen testing; mutagens; neoplasm /cancer genetics; opossums; polymerase chain reaction; radiation carcinogen; radiation carcinogenesis; radiation genetics; skin hyperplasia; skin pharmacology; tumor suppressor genes; ultraviolet radiation

The long-term objective of this research is to identify risk factors and underlying mechanisms for the induction cutaneous melanoma in humans. Specifically. studies outlined in this proposal will (a) determine the effectiveness of UV-A (320-400nm) radiation in the induction of melanoma and (b) identify a role for alterations in tumor suppressor genes in UV-A-induced melanoma. The rationale for these studies is that human exposure to UV-A may be increasing due to the use of chemical sunscreens that primarily block UV-B (280-320 nm) radiation, the most efficient solar wavelengths for the induction of erythema. Thus, the use of sunscreens may result in increased exposure to UV-A due to extended hours spent outdoors. In addition, in recent years, high intensity UV-A radiation sources have replaced artificial sources of UV-B for use in tanning. Individuals using these devices experience increased levels of UV-A exposure. Even small increases in UV-A exposure could result in significant increases melanoma if melanoma induction is more efficient than the induction of erythema or non-melanoma skin cancer these wavelengths. Studies by others with a fish model predict a high efficiency for melanoma induction by UV-A wavelengths. Results from studies proposed herein will be extremely valuable for (1) evaluating the capacity sunscreens to prevent melanoma, (2) determining the potential risk of melanoma induction associated with the use of UV-A-emitting tanning devices, and (3) identifying molecular mechanisms of melanoma induction. The role of UV-A radiation in the induction of melanoma will be determined using a South American opposum, Monodelphis domestica, that is susceptible to the induction of cutaneous melanoma upon chronic exposure to UVR alone. Groups of opossums will be exposed to graded doses of UV-A three times per week for up to 104 wee Animals will be monitored to determine (1) the time to appearance of melanocytic hyperplasia, the putative precursor of melanoma, (2) the progression of melanocytic hyperplasia to melanoma, and (3) the time appearance and yield of non-melanoma skin tumors. Two-stage initiation-promotion studies will be conducted determine the capacity of UV-A to promote the formation of melanoma in dimethylbenzanthracene (DMBA)-initiate skin. In addition, alterations (mutations, deletions and methylation) in p16 and p53 tumor suppressor genes will measured in genomic DNA from melanomas induced with UV-B, UV-A and DMBA. Archival melanoma samples from previous UV-B and DMBA studies are available to initiate tumor suppressor gene analysis.

这项研究的长期目标是确定风险因素 以及诱导皮肤黑色素瘤的基本机制 人类。具体来说。该提案中概述的研究将（a） 确定UV-A（320-400Nm）辐射在 诱导黑色素瘤和（b）确定改变的作用 UV-A诱导的黑色素瘤中的肿瘤抑制基因。理由 这些研究是，人类对UV-A的接触可能会增加 使用主要阻止UV-B的化学防晒霜（280-320 NM）辐射，是最有效的太阳波长 诱导红斑。因此，使用防晒霜可能会导致 由于在户外度过的时间长时间，增加了UV-A的接触。在 此外，近年来，高强度UV-A辐射源 已经取代了用于晒黑的UV-B的人工来源。 使用这些设备的个人经历了UV-A的水平增加 接触。即使是紫外线A暴露的少量增加也可能导致 如果黑色素瘤诱导更多 高效诱导红斑或非黑色素瘤皮肤癌 这些波长。其他人使用鱼类模型的研究预测 UV-A波长诱导黑色素瘤的高效率。 结果 从本文提出的研究中，对于（1）将非常有价值 评估可预防黑色素瘤的容量防晒霜，（2） 确定与 使用UV-A发射晒黑设备，以及（3）识别 黑色素瘤诱导的分子机制。 UV-A的角色 黑色素瘤诱导中的辐射将使用A 南美对比，易感 在慢性暴露于UVR时诱导皮肤黑色素瘤 独自的。负鼠组将暴露于分级剂量的UV-A 每周三次，最多将监视104个魏动物 确定（1）出现黑素细胞增生的时间， 黑色素瘤的推定前体，（2）黑素细胞的进展 对黑色素瘤的增生，（3） 非黑色素瘤皮肤肿瘤。两阶段启动促进研究 将进行确定UV-A促进的能力 在二甲基苯甲烷（DMBA）生效中形成黑色素瘤 皮肤。此外，变化（突变，缺失和 P16和p53肿瘤抑制基因中的甲基化将在 用UV-B，UV-A和DMBA诱导的黑色素瘤的基因组DNA。 来自以前UV-B和DMBA研究的档案黑色素瘤样品是 可用于启动肿瘤抑制基因分析。