Developmental Immunotoxicity of Atrazine

描述：阿特拉津是美国使用最广泛的单一除草剂，估计每年约有8200万磅用于农作物。在美国的水中检测到它的频率很高，在许多主要的采集器中也检测到了它。因此，农场家庭可能在生长季节或全年暴露于某种浓度的阿特拉津。尽管阿特拉津的使用量很高，但关于其毒性的已发表报告相对较少。此外，我们只能找到一份关于阿特拉津免疫毒性的已发表报告。这份报告显示，在单剂量阿特拉津给药后40天，一次抗体反应持续下降。其他免疫参数表现出更多的瞬时效应。因此，阿特拉津对成年暴露的动物具有免疫毒性。许多物质在动物怀孕期间服用时，已被证明具有更大或不同的免疫毒性。阿特拉津的使用量非常高，而且妇女在怀孕期间摄入阿特拉津的可能性很大，这为确定阿特拉津是否会影响免疫系统的正常发育创造了一个案例。因此，这项申请旨在检验这一假设，即产前暴露于阿特拉津将对免疫系统的正常发育产生不利影响。这一假设将通过让怀孕的小鼠在整个妊娠期暴露于阿特拉津来检验。这些母鸡的后代将被允许哺乳它们的亲生母亲，在出生21天时断奶，并将从6周大的时候开始评估各种免疫参数。这复制了人类在怀孕期间摄取阿特拉津的范例，哺乳孩子，然后评估年轻成年后代的免疫反应。这一R21应用将被用来检验上述假说，并提供数据，以证明产前暴露于阿特拉津对发育免疫反应的影响的机制研究的合理性。

DESCRIPTION: Atrazine is the most heavily used single herbicide in the USA with estimates of approximately 82 million pounds applied to crops each year. It has been detected with very high frequency in the water in the USA as well in many major aquifiers. Thus, farm families are likely exposed to some concentration of atrazine per os during a growing season and perhaps throughout the year. There is a relative paucity of published reports on the toxicity of atrazine despite its very high usage. Also, we were only able to find one published report on the immunotoxicity of atrazine. This report showed a persistent decrease in primary antibody response up to 40 days after the administration of a single dose of atrazine. Other immune parameters showed more transient effects. Thus, atrazine is immunotoxic in an adult exposed animal. Many substances have been shown to have greater or different immunotoxicity when administered during the gestation of the animal. The very high use levels of atrazine and the potential for women to ingest atrazine during the gestational development of their child create a case to determine whether atrazine can affect the normal development of the immune system. Therefore, this application seeks to test the hypothesis that prenatal exposure to atrazine will adversely affect the normal development of the immune system. This hypothesis will be tested by exposing gravid mice to atrazine throughout the gestational period. The offspring of these dams will be allowed to nurse their natural mother, weaned at d21 of life and a variety of immune parameters will be assessed beginning at 6 weeks of age. This duplicates the paradigm of a human ingesting atrazine during the gestation of her child, nursing the child and then assessing the immune response of the young adult offspring. This R21 application will be used to test the above stated hypothesis and provide data to justify mechanistics studies on the effect of prenatal atrazine exposure on the developmental immune response.