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