INDUCTION OF MELANOMA WITH UV-A

UV-A 诱导黑色素瘤

• 批准号: 2895510
• 负责人: RONALD D LEY
• 金额: $ 22.25万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 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 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2895510
• 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 和诱导皮肤黑色素瘤的潜在机制， 人类具体来说本建议概述的研究将（a） 确定UV-A（320- 400 nm）辐射在 黑色素瘤诱导和（B）鉴定改变在 肿瘤抑制基因在UV-A诱导的黑色素瘤中的作用的理由 这些研究表明，人类暴露于UV-A可能会增加， 使用主要阻挡UV-B（280-320 nm）辐射，最有效的太阳波长为 诱发红斑。因此，使用防晒霜可能会导致 由于长时间在户外，暴露于UV-A的时间增加。在 此外，近年来，高强度UV-A辐射源 已经取代了人工来源的紫外线-B用于制革。 使用这些设备的人会经历更高水平的UV-A exposure.即使是紫外线A暴露的微小增加也可能导致 如果黑色素瘤诱导更多， 比诱发红斑或非黑色素瘤皮肤癌有效 这些波长。其他人用鱼类模型进行的研究预测， UV-A波长对黑色素瘤诱导效率高。 结果 从本文提出的研究将是非常有价值的（1） 评估防晒霜预防黑色素瘤的能力，（2） 确定黑色素瘤诱导的潜在风险， 使用发射紫外线A的晒黑设备，以及（3）识别 黑色素瘤诱导的分子机制UV-A的作用 辐射在黑色素瘤诱导中的作用将使用 南美的对生种，南美单甲鲶， 在长期暴露于UVR时诱导皮肤黑色素瘤 一个人各组负鼠将暴露于不同剂量的UV-A 每周三次，最多104只动物将被监测， 确定（1）黑素细胞增生出现的时间， 假定的黑色素瘤前体，（2）黑色素细胞的进展 增生到黑色素瘤的时间和产量，（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的能力，以促进 二甲基苯并蒽（DMBA）引发的黑色素瘤形成 皮肤此外，改变（突变、缺失和 p16和p53肿瘤抑制基因中的甲基化）将在 来自用UV-B、UV-A和DMBA诱导的黑素瘤的基因组DNA。 来自先前UV-B和DMBA研究的存档黑色素瘤样品是 启动肿瘤抑制基因分析。