Developmental Immunotoxicity of Atrazine

描述：阿特拉津是美国使用最多的单一除草剂，估计每年约有8200万磅用于农作物。在美国以及许多主要的蓄水器中，它已被检测到非常高的频率。因此，农民家庭可能在生长季节甚至全年都接触到一定浓度的阿特拉津。尽管阿特拉津的使用率很高，但有关其毒性的已发表报告相对较少。而且，我们只能找到一份关于阿特拉津免疫毒性的公开报告。本报告显示，一抗反应在单剂量阿特拉津治疗后持续下降至40天。其他免疫参数表现出更短暂的影响。因此，阿特拉津对接触的成年动物具有免疫毒性。许多物质在动物妊娠期间施用时显示出更大或不同的免疫毒性。阿特拉津的高使用量以及妇女在孩子妊娠发育期间摄入阿特拉津的可能性使人们有理由确定阿特拉津是否会影响免疫系统的正常发育。因此，本应用程序旨在测试假设，即产前暴露于阿特拉津会对免疫系统的正常发育产生不利影响。这一假设将通过将妊娠小鼠在整个妊娠期暴露于阿特拉津来验证。这些水坝的后代将被允许喂养它们的生母，在21岁时断奶，并在6周龄开始评估各种免疫参数。这重复了一个人在怀孕期间摄入阿特拉津，喂养孩子，然后评估年轻成年后代的免疫反应的范例。该R21申请将用于测试上述假设，并提供数据来证明产前接触阿特拉津对发育免疫反应影响的机制研究。

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.