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Evaluation of dioxins contamination to the large field mouse, Apodemus speciosus

大田鼠黑线姬鼠二恶英污染评价

基本信息

批准号：
16580119
负责人：
SEKIJIMA Tsuneo
金额：
$ 2.37万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580119/
关键词：
Dioxin Apodemus speciosus Aryl hydrocarbon receptor Sperm activity Polymorphism transcriptional activity Aryl hydrocarbon Receptor ダイオキシン感受性 AhR 精子数

项目摘要

Polychlorinated dibezo-p-dioxins (PCDDs), polychrorinated dibenzofurans (PCDFs) and dioxin-like poly chrorinated dibenzofurans (dioxine-like PCBs), which are generically called as dioxins, are highly toxic and persistent lipophilic substances. These compounds are mainly produced in the process of incineration for industrial waste products or burning on the filled-up land for such products, and then are released into soil and air. These are known to bioaccumulate up the food chain and damage to reproductive activities of higher consumers in food web. Recently, however, it have been reported that the Japanese large field mouse, Apodemus speciosus, which have been regarded as comparatively lower consumer, had the highest accumulation of dioxins among mammals in a food web including higher consumers such as fox and weasel, which means that this species become an effective biomarker for evaluating an effect of dioxins contamination to wildlives. Dioxins cause various biological and toxicolo … More gical responses, typified by teratogenesis, thymic atrophy, severe epithelial disorders, wasting symdrome, tumore promotion, and induction of drug-metabolizing enzymes in experimental animals. Furthermore, the hormonal acts that dioxins exhibit make the endocrine system of animals disrupt and consequently cause abnormal sexual gland and decreased sperm counts.To clarify physiological and ecological effects of dioxins exposure on wild populations of A.speciosus, we firstly investigated the relationship between dioxins concentration in soil and its accumulation level in mouse liver, and the relationships between dioxins accumulation in mouse and sperm activity, or sperm counts, in adult male A.speciosus. Next, we analyzed polymorphism and its functional difference in aryl hydrocarbon receptor (AhR) of A.speciosus, which is well known as the receptor of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice and soils were collected from seven points ; four points in Niigata prefecture, one in Yamagata prefecture, one in Saitama prefecture, and one in Fukuoka prefecture. No significant correlation found between concentrations of dioxins in soils and dioxin accumulation levels in mice, although dioxin accumulations in mice tended to increase with dioxin concentrations in soils. On the other hand, the sperm activity and sperm count were decreased with dioxin accumulation, in the case except for the highest study site of dioxin contamination. Primary structure of A speciosus AhR was extremely variable. The mutations were concentrated in two regions, i.e. between PAS-A and PAS-B, and transactivation domain. A.speciosus AhR showed high transcriptional activity in response to 3MC. One mutation of Q799 to R in transactivation domain decreased activity. On the other hand, there was no difference in transcriptional activity among mutations in PAS domain.In conclusion, dioxins may disrupt the endocrine system of A.speciosus and AhR having high intraspecific variation may become an effective molecular marker to evaluate effect of dioxins at population level. Less

多氯二苯并对二恶英（PCDD）、多氯二苯并呋喃（PCDF）和二恶英类多氯二苯并呋喃（二恶英样PCB）统称为二恶英，是剧毒、持久性亲脂性物质。这些化合物主要是在工业废物焚烧或工业废物填埋地燃烧过程中产生的，然后释放到土壤和空气中。众所周知，这些物质会在食物链中生物累积，并损害食物网中高级消费者的生殖活动。然而，最近有报道称，一直被认为较低级消费者的日本大田鼠Apodemus spiosus，在包括狐狸和黄鼠狼等较高级消费者在内的食物网哺乳动物中，二恶英累积量最高，这意味着该物种成为评估二恶英污染对野生动物影响的有效生物标志物。二恶英会引起各种生物和毒理学反应，典型的是实验动物中的致畸、胸腺萎缩、严重上皮疾病、消耗综合征、促进肿瘤和药物代谢酶的诱导。此外，二恶英所表现出的激素作用会扰乱动物的内分泌系统，从而导致性腺异常和精子数量减少。为了阐明二恶英暴露对白花姬蜂野生种群的生理和生态影响，我们首先研究了土壤中二恶英浓度与其在小鼠肝脏中积累水平之间的关系，以及小鼠体内二恶英积累与精子活性之间的关系，或成年雄性 A.speciosus 的精子计数。接下来，我们分析了A.speciosus芳烃受体(AhR)的多态性及其功能差异，AhR是众所周知的2,3,7,8-四氯二苯并-对二恶英(TCDD)受体。从七个点收集小鼠和土壤；新泻县4处、山形县1处、埼玉县1处、福冈县1处。尽管小鼠体内二恶英累积量随着土壤中二恶英浓度的增加而增加，但土壤中二恶英浓度与小鼠体内二恶英累积水平之间没有发现显着相关性。另一方面，除了二恶英污染最高的研究点外，精子活力和精子数量随着二恶英的积累而降低。 A spiosus AhR 的一级结构变化极大。突变集中在两个区域，即PAS-A和PAS-B之间以及反式激活结构域。 A.speciosus AhR 对 3MC 表现出高转录活性。反式激活结构域中 Q799 突变为 R，活性降低。另一方面，PAS结构域突变之间的转录活性没有差异。综上所述，二恶英可能会扰乱A.speciosus的内分泌系统，而具有高种内变异的AhR可能成为评估二恶英在群体水平上的影响的有效分子标记。较少的