Wang J S, Busby W F, Wogan G N
Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
Toxicol Appl Pharmacol. 1990 May;103(3):430-40. doi: 10.1016/0041-008x(90)90316-m.
A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels (1.5-3.5% of dose) over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content (carcass, skin) or the absorption (stomach, small intestine), metabolism (liver), or excretion (kidney) of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity (dpm/g tissue) instead, the carcass and skin dropped from the top rank tissues at 90 min and were replaced by the spleen and cecum. At 24 hr and 7 days the top-ranked order of tissues shifted to include organs associated with trichothecene-induced toxicity such as the lymphohematopoietic system (spleen, thymus, and femur bone marrow), heart, and testis (in mouse) as well as the cecum and large intestine. In addition, the rate of loss of radioactivity with time generally did not decrease as rapidly in these target organs as observed in liver, kidney, skin, and carcass. Brain radioactivity, though very low, also diminished relatively slowly. Significant differences in specific radioactivity which did occur between the rat and mouse tended to occur in target organs and with the higher levels present in the mouse. These data were discussed in terms of interspecies differences in lethality and target organ toxicity.
在大鼠和小鼠中，对口服亚致死剂量的[3H]二乙酰氧基镰刀菌烯醇（安圭定）后90分钟、24小时和7天的组织分布和排泄情况进行了定量比较。总回收率达到95 - 100%。在最初的24小时内，约90%的剂量通过尿液和粪便排出，两种动物的粪便与尿液比例约为1:4.5。在最初的24小时内， carcass和组织放射性迅速下降，但在实验过程中保持相对稳定的低水平（剂量的1.5 - 3.5%）且可检测到。在组织分布方面未观察到明显的种间差异。90分钟时，剂量占比最高的组织是那些因高含水量/脂质含量（ carcass、皮肤）或毒素吸收（胃、小肠）、代谢（肝脏）或排泄（肾脏）而参与二乙酰氧基镰刀菌烯醇隔离的组织。在实验过程中，这些组织的排序通常是稳定的。当数据以比放射性（dpm/g组织）表示时， carcass和皮肤在90分钟时从排名靠前的组织中掉出，被脾脏和盲肠取代。在24小时和7天时，排名靠前的组织顺序发生变化，包括与单端孢霉烯族毒素诱导毒性相关的器官，如淋巴造血系统（脾脏、胸腺和股骨骨髓）、心脏以及小鼠的睾丸，还有盲肠和大肠。此外，这些靶器官中放射性随时间的损失速率通常不像在肝脏、肾脏、皮肤和 carcass中观察到的那样迅速下降。脑放射性虽然很低，但下降也相对缓慢。大鼠和小鼠之间确实出现的比放射性显著差异往往出现在靶器官中，且小鼠中的水平更高。根据种间在致死率和靶器官毒性方面的差异对这些数据进行了讨论。
