INDUCTION OF MELANOMA WITH UV-A

UV-A 诱导黑色素瘤

• 批准号: 2739731
• 负责人: RONALD D LEY
• 金额: $ 19.78万
• 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/2739731
• 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。 和诱发皮肤黑色素瘤的潜在机制 人类。具体地说。这项建议中概述的研究将：(A) 确定UV-A(320-400 nm)辐射在 黑色素瘤的诱导和(B)确定改变在 紫外线-A诱导黑色素瘤中的肿瘤抑制基因。其基本原理是 这些研究表明，人类暴露在UV-A下的风险可能正在增加 使用主要阻挡紫外线B的化学防晒霜(280-320 毫微米)辐射，最有效的太阳波长 诱发红斑。因此，使用防晒霜可能会导致 由于长时间的户外活动，暴露在UV-A下的时间增加。在……里面 此外，近年来，高强度UV-A辐射源 已经取代了人造的UV-B来源，用于制革。 使用这些设备的人会感受到更高水平的UV-A 曝光。即使紫外线-A暴露的微小增加也可能导致 如果黑色素瘤诱导率较高，则显著增加黑色素瘤 比诱发红斑或非黑色素瘤皮肤癌更有效 这些波长。其他人用鱼模型进行的研究预测了 UV-A波长诱导黑色素瘤的高效率。结果 从这里提出的研究将非常有价值的(1) 评估防晒霜预防黑素瘤的能力，(2) 确定与以下因素相关的诱发黑色素瘤的潜在风险 使用UV-A发射的制革设备，以及(3)识别 黑色素瘤诱导的分子机制。UV-A的作用 诱发黑色素瘤的辐射将使用 易感的南美对虾--家养斑潜蝇 紫外线慢性照射诱发皮肤黑色素瘤的研究 独自一人。负鼠群体将暴露在分级剂量的UV-A下 每周对最多104只幼崽进行三次监测，以 测定(1)黑素细胞增生出现的时间， 推测为黑色素瘤的前体，(2)黑素细胞的进展 从增生到黑色素瘤，以及(3)出现和转移的时间。 非黑色素瘤皮肤肿瘤。两阶段启蒙促进研究 将进行UV-A能力测定，以促进 二甲基苯并菲(DMBA)引发黑色素瘤的形成 皮肤。此外，改变(突变、缺失和 P16和p53抑癌基因的甲基化)将在 UV-B、UV-A和DMBA诱导黑色素瘤基因组DNA的研究 来自之前UV-B和DMBA研究的黑色素瘤档案样本是 可用于启动肿瘤抑制基因分析。