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[多氯联苯对小鼠和大鼠肝脏微粒体酶的诱导作用及其与组织中多氯联苯水平的关系]

[Induction of mouse and rat liver microsomal enzymes by polychlorinated biphenyls and its relations to the PCB levels in the tissue].

作者信息

Shimada T, Nunoura Y, Kitanaka E, Iwagami S, Mizuta Y

出版信息

Nihon Yakurigaku Zasshi. 1976 Nov;72(8):955-67. doi: 10.1254/fpj.72.955.

Abstract

Kanechlor (KC)-300, 400, 500, and 600 consisting of polychlorinated biphenyls (PCB) containing 43, 48, 55, and 61% chlorine respectively, were administered in a single dose of 100 mg/kg to mice and rats. The effect of PCB was investigated by determining pentobarbital sleeping time, liver microsomal hemoprotein contents, PCB level and gaschromatography (GC) pattern in tissue. Pentobarbital sleeping time was prolonged 2 to 4 times longer than that of control level after 3 to 4 hr of KC treatment in both ICR and ddN strain mice and KC-300 was the most effective. Forty-eight hr after treatment, however, this sleeping time was half that of the control. Sleeping time in ICR strain mice returned to control level 8 days after the treatment with KC-300 and KC-500, but the decrease in sleeping time continued in ddN mice. Conversely, the prolongation of sleeping time in rats was only 20% the control level at 3 hr after KC-300 treatment, but the shortening of sleeping time was more marked than in mice. Both the prolongation of sleeping time in mice treated with KC-300 and the shortening of sleeping time in rats treated wiht KC-500 were more rapidly effected when an oral dose rather than when a intraperitoneal one was given. Induction of liver microsomal cytochrome P-450 level was maximum in rats treated with KC-600 and increase of hemoprotein level and shortening of sleeping time were proportional to the chlorine content of PCB. The CO-difference spectrum of microsomes from rats treated with KC had an absorbance maximum at 448 nm. Direct relationship between storage of PCB in adipose tissue and the induced effect by KC has also been demonstrated in rats. PCB level in the liver of rats was higher for about 8 hr after KC-500 treatment given orally and was lower than the PCB level in adipose tissue after 8 hr. The GC-pattern of PCB stored in tissues was different from that of standard KC, indicating that all components were not metabolized at the same rate and that the components of the KC with the longer retention time were metabolized to a lesser degree than those with the shorter retention time.

摘要

分别含有43%、48%、55%和61%氯的多氯联苯(PCB)组成的凯恩氯(KC)-300、400、500和600,以100毫克/千克的单剂量给予小鼠和大鼠。通过测定戊巴比妥睡眠时间、肝微粒体血红蛋白含量、组织中的PCB水平和气相色谱(GC)图谱来研究PCB的作用。在ICR和ddN品系小鼠中,KC处理3至4小时后,戊巴比妥睡眠时间比对照水平延长了2至4倍,且KC-300最为有效。然而,处理48小时后,该睡眠时间仅为对照的一半。用KC-300和KC-500处理后8天,ICR品系小鼠的睡眠时间恢复到对照水平,但ddN小鼠的睡眠时间持续减少。相反,KC-300处理3小时后,大鼠睡眠时间的延长仅为对照水平的20%,但睡眠时间的缩短比小鼠更明显。当给予口服剂量而非腹腔注射剂量时,用KC-300处理的小鼠睡眠时间延长和用KC-500处理的大鼠睡眠时间缩短的效果更快。用KC-600处理的大鼠肝微粒体细胞色素P-450水平的诱导最大,血红蛋白水平的增加和睡眠时间的缩短与PCB的氯含量成正比。用KC处理的大鼠微粒体的CO-差光谱在448纳米处有最大吸光度。在大鼠中也证明了PCB在脂肪组织中的储存与KC的诱导作用之间的直接关系。口服给予KC-500后,大鼠肝脏中的PCB水平在约8小时内较高,8小时后低于脂肪组织中的PCB水平。组织中储存的PCB的GC图谱与标准KC的不同,表明所有成分的代谢速率不同,且保留时间较长的KC成分的代谢程度低于保留时间较短的成分。

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