Giri S N, Siegel D M, Peoples S A
Toxicology. 1978 Oct;11(2):153-65. doi: 10.1016/s0300-483x(78)90989-7.
The avicide [14C]3-chloro-p-toluidine (CPT) HCL, ring labeled, was injected intravenously to mice. The radioactivity associated with this compound was found to be unevenly distributed in different parts of the body. It leaves the plasma, as well as many tissues, with 2 elimination rate constants, the fast and the slow. The faster component of the [14C]CPT decay curve of the plasma was similar to the faster components of the decay curves of brain, lung, heart, intestine, testicle and kidney. The retention half-life of the radioactivity for the slower component of the decay curve varied a great deal from tissue to tissue, being shortest (14.55 h) in the intestine and longest (326 h) in the adipose tissue. Of the 10 tissues examined, a substantial amount of [14C]CPT radioactivity was found to be covalently bound only to liver, kidney, lung and RBC protein. There was no cause and effect relationship between the covalent binding of radioactivity and the tissue pathology, since no remarkable histopathological lesions were found in the liver and kidney of treated mice. The tissue retention of [14C]CPT radioactivity did not parrallel the covalent binding of the compound to tissue protein. The covalent binding of [14C]CPT radioactivity to RBC was suggestive of the conversion of the parent compound into a reactive metabolite responsible for the generation of methemoglobin in mice. The percent distribution of radioactivity in subcellular fractions of liver and kidney correlated with the amount of protein associated with subcellular fractions. The 102 000 g supernatant fraction of the liver contained the highest proportion of radioactivity, both in terms of absolute percent radioactivity as well as specific activity (dpm/mg of protein). This was also true for the 102 000 g supernatant fraction of the kidney. The majority of radioactivity in the 102 000 g supernatant fraction of liver appears to be bound to one or more polypeptide sized proteins with a mol. wt. of approx. 1000--2000.
将环标记的杀鸟剂[14C]3-氯-对甲苯胺（CPT）盐酸盐静脉注射到小鼠体内。发现与该化合物相关的放射性在身体不同部位分布不均。它以快速和缓慢两个消除速率常数离开血浆以及许多组织。血浆中[14C]CPT衰变曲线的较快成分与脑、肺、心脏、肠道、睾丸和肾脏衰变曲线的较快成分相似。衰变曲线较慢成分的放射性保留半衰期因组织而异，在肠道中最短（14.55小时），在脂肪组织中最长（326小时）。在所检查的10个组织中，发现大量[14C]CPT放射性仅与肝脏、肾脏、肺和红细胞蛋白共价结合。放射性的共价结合与组织病理学之间没有因果关系，因为在处理过的小鼠的肝脏和肾脏中未发现明显的组织病理学损伤。[14C]CPT放射性的组织保留与该化合物与组织蛋白的共价结合不平行。[14C]CPT放射性与红细胞的共价结合表明母体化合物转化为一种活性代谢物，该代谢物导致小鼠体内高铁血红蛋白的产生。肝脏和肾脏亚细胞组分中放射性的百分比分布与与亚细胞组分相关的蛋白质量相关。肝脏102 000g上清液组分无论是绝对放射性百分比还是比活性（dpm/毫克蛋白）都含有最高比例的放射性。肾脏102 000g上清液组分也是如此。肝脏102 000g上清液组分中的大部分放射性似乎与一种或多种分子量约为1000 - 2000的多肽大小的蛋白质结合。
