UVR-INDUCED DNA DAMAGE AND ANGIOGENIC GROWTH FACTORS
紫外线引起的 DNA 损伤和血管生成因子
基本信息
- 批准号:3265705
- 负责人:
- 金额:$ 11.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-05-01 至 1995-04-30
- 项目状态:已结题
- 来源:
- 关键词:DNA damage DNA repair angiogenesis angiogenesis factor cornea disorder corneal epithelium endodeoxyribonuclease gel electrophoresis genetic library histopathology immunocytochemistry in situ hybridization lens northern blottings nucleic acid probes opossums protein biosynthesis pyrimidine dimers radiation carcinogen radiation carcinogenesis solar radiation ultraviolet radiation
项目摘要
Skin and eyes are the only organs of the body that are exposed directly to
solar ultraviolet radiation (UVR). It has been shown that xeroderma
pigmentosum individuals are deficient in DNA repair and have an increased
susceptibility to UVR-induced opacification and neovascularization of the
cornea and cancer of the anterior eye. The prospect of stratospheric ozone
depletion and the accompanying increase in human exposure to UVR makes it
imperative that we understand the acute and chronic responses of the
mammalian eye to UVR exposure. The marsupial Monodelphis domestica is an
experimental animal model uniquely suited for studies on the role of a
specific UVR-induced DNA lesion, the pyrimidine dimer, in causing
pathological changes in eyes exposed to UVR. As in the epidermis, cells in
the corneal epithelium of M. domestica have a high capacity for the
photoreactivation (PR) repair of UVR-induced pyrimidine dimers. The
light-dependent PR repair pathway has the unique property of repairing only
pyrimidine dimers; therefore, if PR decreases the ability of UVR to induce
a photobiological response, it is generally accepted that pyrimidine dimers
are in some way involved in initiating that response.
Chronic UVR exposure of M. domestica induces tumors of the cornea. UVR
induces proliferation of corneal stromocytes and endothelial cells which
precedes tumor development. It seems reasonable to assume that UVR in some
way induces the synthesis or secretion of mitogenic and angiogenic growth
factors that act in an autocrine or paracrine manner to stimulate
proliferation of corneal stromocytes and endothelial cells. The proposed
research will lest the hypothesis that unrepaired pyrimidine dimers in DNA
alters the synthesis and/or release of mitogenic and angiogenic growth
factors in the UVR-exposed cornea. These early molecular events may result
in enhanced susceptibility to UVR-induced cancer. The specific aims are:
1) RNA blotting and standard histological techniques will be used to
determine the time course of angiogenic growth factor expression and
pathological changes that occur in the chronically-irradiated cornea. PR
will be used to define a role for DNA damage in these processes; 2) in situ
hybridization and immunohistochemical staining will be used to identify the
site of synthesis and/or release of angiogenic growth factors in the
chronically irradiated cornea; and, 3) as an extension of studies on DNA
repair in corneal epithelium, damage-specific nucleases in conjunction with
alkaline gel electrophoresis will be used to measure the excision and
photoreactivation repair of UVR-induced pyrimidine dimers in lens
epithelial DNA.
皮肤和眼睛是人体唯一直接接触到的器官
项目成果
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{{ truncateString('RONALD D LEY', 18)}}的其他基金
UVR-INDUCED SYSTEMIC EFFECTS AND MELANOMA INDUCTION
紫外线引起的系统效应和黑色素瘤诱导
- 批准号:
2099091 - 财政年份:1992
- 资助金额:
$ 11.78万 - 项目类别:
UVR-INDUCED DNA DAMAGE AND ANGIOGENIC GROWTH FACTORS
紫外线引起的 DNA 损伤和血管生成因子
- 批准号:
3265704 - 财政年份:1992
- 资助金额:
$ 11.78万 - 项目类别:
UVR-INDUCED SYSTEMIC EFFECTS AND MELANOMA INDUCTION
紫外线引起的系统效应和黑色素瘤诱导
- 批准号:
3202548 - 财政年份:1992
- 资助金额:
$ 11.78万 - 项目类别:
UVR-INDUCED DNA DAMAGE AND ANGIOGENIC GROWTH FACTORS
紫外线引起的 DNA 损伤和血管生成因子
- 批准号:
2162234 - 财政年份:1992
- 资助金额:
$ 11.78万 - 项目类别:
UVR-INDUCED SYSTEMIC EFFECTS AND MELANOMA INDUCTION
紫外线引起的系统效应和黑色素瘤诱导
- 批准号:
2099092 - 财政年份:1992
- 资助金额:
$ 11.78万 - 项目类别:
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