RIBONUCLEOSIDES FOR PREDICTION OF SKIN IRRITATION

用于预测皮肤刺激的核糖核苷

• 批准号: 6022235
• 负责人: WILLIAM G REIFENRATH
• 金额: $ 10万
• 依托单位: STRATACOR, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6022235
• 关键词: DNA damage; biomarker; diagnosis design /evaluation; high performance liquid chromatography; lactate dehydrogenases; nucleic acid metabolism; pyrimidine nucleosides; receptor expression; ribonucleosides; skin irritation /irritant; swine; technology /technique development; tissue /cell culture

Biochemical measurements of skin integrity were conducted to measure the skin s response to toxic chemicals, which included aqueous solutions of sodium fluoride or lead acetate, and xylene solution of benzo [a] pyrene as positive controls. Receptor fluid bathing the visceral side of excised pig skin was assays for lactate production as an indicator of the main energy- producing pathways, for the enzyme lactic acid dehydrogenase (LDH) as an indicator of cell lysis, for color changes in a redox dye to indicate alteration in the oxidation-reduction capacity of the tissue, for RNA nucleosides as an indicator of aberrant RNA metabolism, and for accumulation of mutagenic products. Alteration of pyrimidine nucleoside excretion by skin was the most sensitive indicator of exposure to chemical or biological insults. We propose that alterations in ribonucleosides from excised skin will serve as sensitive indicators of exposure to skin irritants. We further propose to conduct such tests using a novel diffusion cell array based on standard 24 well culture plates. PROPOSED COMMERCIAL APPLICATION Development of new materials that contact the skin (e.g. topical drugs, cosmetics) usually requires an assessment of skin irritation potential in an animal model. There is a demand in commerce for an in vitro test that would reduce animal usage and produce results more predictive for man. Development of our technology will provide such a test with significant advantages over currently available test kits.

进行皮肤完整性的生化测量以测量皮肤对有毒化学物质的反应，其中包括氟化钠或乙酸铅的水溶液，以及苯并[a]芘的二甲苯溶液作为阳性对照。 测定了浸泡离体猪皮内脏侧的受体液的乳酸盐产生（作为主要能量产生途径的指示剂）、乳酸脱氢酶（LDH）（作为细胞裂解的指示剂）、氧化还原染料的颜色变化（指示组织氧化还原能力的改变）、RNA核苷（作为异常RNA代谢的指示剂）以及致突变产物的蓄积。皮肤嘧啶核苷排泄的改变是暴露于化学或生物损伤的最敏感指标。 我们建议，从切除的皮肤中的核糖核苷的改变将作为暴露于皮肤刺激物的敏感指标。 我们还建议使用基于标准24孔培养板的新型扩散池阵列进行此类测试。拟定的商业应用开发与皮肤接触的新材料（例如局部药物、化妆品）通常需要在动物模型中评估皮肤刺激潜力。 商业上需要一种能减少动物使用并产生对人更有预测性的结果的体外试验。我们技术的发展将为这种试验提供比目前可用的试验试剂盒更显著的优势。