FETAL ALCOHOL EXPOSURE AND TUMORIGENESIS

胎儿酒精暴露与肿瘤发生

• 批准号: 3422062
• 负责人: ZEHAVA GOTTESFELD
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422062
• 关键词: alcoholism /alcohol abuse; bacterial disease; blood chemistry; cellular immunity; chromatography; corticosterone; disease /disorder proneness /risk; drug abuse; drug related neoplasm /cancer; estrogens; fetal alcohol syndrome; flow cytometry; hormone therapy; immunosuppression; laboratory rat; longitudinal animal study; neuroendocrine system; parent offspring interaction; pituitary neoplasms; prenatal stress; prolactin; radioimmunoassay; statistics /biometry

Clinical studies have suggested that prenatal alcohol exposure is associated with increased risk of tumorigenesis. Immune defects may account for this abnormality, since the immune system plays a pivotal role in cancer and infectious diseases (e.g. AIDS). Preliminary studies in this laboratory have shown that young adult rodents which were exposed to alcohol in utero display increased susceptibility to estrogen-induced pituitary tumors (prolactinoma) and a further enhancement of immune suppression. The mechanisms which underlie these abnormalities are not known, but the recognition of neuro-immune-endocrine interactions may be relevant. Thus, the long-term objective of this research proposal is to elucidate the neuroendocrine and immune mechanisms which underlie the increased susceptibility to tumor induction of offspring born to alcohol- abusing mothers. Specifically, the first aim of the proposed project is to further characterize the effects of prenatal alcohol exposure on the immunologic and neuroendocrine responses to short- and long-term estrogen treatments of the Fischer 344 rat. The second aim is to determine the persistency of pituitary tumors as well as of the immune and neuroendocrine responses following termination of estrogen treatments. Parameters to be measured include pituitary tumor size, cellular immune response and neuroendocrine variables such as prolactin and corticosterone. The proposed research will contribute to the understanding of mechanisms by which alcohol abuse during pregnancy elicits neuroendocrine and immune defects, thus compromising the well being of the offspring throughout life.

临床研究表明，产前酒精暴露是 与肿瘤发生风险增加有关。 免疫缺陷可能 说明这种异常，因为免疫系统起着关键作用 在癌症和传染病中（例如艾滋病）。 初步研究 实验室表明，暴露于 子宫内的酒精显示增加了雌激素诱导的易感性 垂体肿瘤（催乳素瘤）和免疫的进一步增强 抑制。 这些异常的基础的机制不是 已知，但对神经免疫 - 内分泌相互作用的认识可能是 相关的。 因此，这项研究建议的长期目标是 阐明神经内分泌和免疫机制，这些机制是 提高了对酒精出生的后代诱导肿瘤的敏感性 - 虐待母亲。 具体而言，拟议项目的第一个目的是 进一步表征了产前酒精暴露对 免疫学和神经内分泌对短期和长期雌激素的反应 Fischer 344大鼠的处理。 第二个目的是确定 垂体肿瘤以及免疫和神经内分泌的持久性 终止雌激素治疗后的反应。 参数为 测得的包括垂体肿瘤大小，细胞免疫反应和 神经内分泌变量，例如催乳素和皮质酮。 拟议的研究将有助于理解机制 怀孕期间哪些酗酒会引起神经内分泌和免疫 缺陷，因此损害了一生中后代的福祉。