The disposition of allyl isothiocyanate in the rat and mouse
The disposition of allyl isothiocyanate in the rat and mouse
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DOI：
10.1016/s0278-6915(97)00103-8
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发表时间：
1997-10-01
影响因子：
4.3
通讯作者：
Caldwell, J
中科院分区：
文献类型：
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作者：
Bollard, M;Stribbling, S;Caldwell, J
雄性和雌性Fischer 344大鼠和B6C3F(1)小鼠口服异硫氰酸烯丙酯(AITC)(2.5和25 mg/kg体重)后，尿液是放射性排泄的主要途径(剂量的50-80%)。在粪便(6-12%)和呼出的空气(3-7%)中发现的量较少。这两个物种之间的主要区别是，与小鼠(剂量的2-5%)相比，大鼠在4天后的放射性保留更大(剂量的18%-24%)。在小鼠和大鼠的尿液中分别发现了三种放射性成分和两种放射性成分。这三种成分分别为无机硫氰酸盐、烯丙基硫代氨基甲酰硫代尿酸和烯丙基硫代氨基甲酰半胱氨酸，而大鼠尿中未发现半胱氨酸结合物。在小鼠中，大约80%的C-14以硫氰酸盐离子的形式存在于尿液中，而在大鼠中，约75%的C-14以硫氰酸盐的形式存在。这表明，在小鼠体内，AITC的主要代谢途径是AITC，而在大鼠体内，谷胱甘肽结合是主要代谢途径。在大鼠和小鼠全血中存在的[C-14]AITC衍生放射性的数量存在物种差异；与小鼠(96小时)相比，大鼠血液中可测量的放射性水平保持了更长的时间(长达240小时)。雄性和雌性大鼠口服[C-14]AITC后的尿囊检查显示，雄性大鼠的膀胱组织中[C-14]AITC和/或其代谢物的含量较高，存在性别差异。在美国国家毒理学计划进行的致癌性研究中，根据已知的膀胱肿瘤的种类和性别特异性进行了讨论，这些肿瘤发生在长期给药给药后，雄性大鼠，而不是雌性大鼠或小鼠，由美国国家毒理学计划进行。(C)1997爱思唯尔科学有限公司。保留所有权利。
The urine was the major route of excretion of radioactivity (50-80% of dose) following the oral administration (2.5 and 25 mg/kg body weight) of allyl[C-14]isothiocyanate (AITC) to male and female Fischer 344 rats and B6C3F(1) mice. Smaller amounts were found in the faeces (6-12%) and expired air (3-7%). The major difference between the two species was the greater retention of radioactivity after 4 days within rats (18-24% of dose) when compared with mice (2-5% of dose). Three radioactive components were found in the urine of mice and two in rats. The three components were inorganic thiocyanate, allylthiocarbamoylmercapturic acid and allylthiocarbamoylcysteine in mice, but no cysteine conjugate was found in rat urine. In the mouse, approximately 80% of the C-14 was present in the urine as the thiocyanate ion whereas in the rat some 75% was as the mercapturate. This indicates that in the mouse, hydrolysis of AITC was the major metabolic pathway whereas in the rat glutathione conjugation was the major route. A species difference was seen in the amount of [C-14]AITC-derived radioactivity present in the whole blood of rats and mice; measurable levels of radioactivity remained within rat blood for a longer time period (up to 240 hr) when compared with mice (96 hr). Examination of the urinary bladders of male and female rats following oral dosing with [C-14]AITC showed a sex difference with greater amounts of [C-14]AITC and/or its metabolites within the bladder tissue of male rats. This data is discussed in terms of the known species-and sex-specificity of the urinary bladder tumours, which occurred after long-term administration to male rats, but not to female rats or mice of either sex, in a carcinogenicity study conducted by the National Toxicology Program in the USA. (C) 1997 Elsevier Science Ltd. All rights reserved.