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[2,3,4,7,8-五氯二苯并呋喃在金黄叙利亚仓鼠体内的组织分布、对肝脏酶的诱导作用及急性毒性]

[Tissue distribution, inductive effect on liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran in Golden Syrian hamsters].

作者信息

Koga N, Nakashima H, Kamimura H, Hokama Y, Yoshimura H

出版信息

Fukuoka Igaku Zasshi. 1989 May;80(5):227-34.

PMID:2744684
Abstract

The hamsters have been known to be the least sensitive mammalian species to the acute toxicity of highly toxic polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the present study, the tissue distribution, inductive effect of liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in male Golden Syrian hamsters were examined. The highest content (about 48% of dose) of PenCDF was found in the liver 5 days after a single i.p. dose of 1.0 mg/kg. The amount ranging about 5 to 10% of dose was also distributed to mesentery, skin and muscle. In liver, the distribution of PenCDF was just parallel to that of cytochrome P-450 (P-450), marker enzymes of liver endoplasmic reticulum, suggesting that PenCDF binds to P-450. The mode of inductive effects of PenCDF in hamsters was 3-methylcholanthrene-type as reported previously in rats. However, the typical enzymes such as benzo(a)pyrene 3-hydroxylase and DT-diaphorase were induced to a relatively less extent than did in rats. In hamsters pretreated with PenCDF at a dose of 0.5 mg/kg, the potent atrophy of thymus and the 3-fold increase of liver lipid peroxide were observed, whereas the body weight gain was not suppressed at all. These results suggest that the induction of liver enzymes and the atrophy of thymus might not be the direct cause of PenCDF-induced lethality in hamsters.

摘要

仓鼠是已知对剧毒多卤代烃(如2,3,7,8 - 四氯二苯并 - p - 二恶英)的急性毒性最不敏感的哺乳动物物种。在本研究中,检测了2,3,4,7,8 - 五氯二苯并呋喃(PenCDF)在雄性金黄地鼠体内的组织分布、对肝酶的诱导作用及急性毒性。单次腹腔注射1.0 mg/kg剂量的PenCDF后5天,肝脏中PenCDF含量最高(约占剂量的48%)。约5%至10%剂量的PenCDF也分布于肠系膜、皮肤和肌肉。在肝脏中,PenCDF的分布与肝脏内质网的标志物细胞色素P - 450(P - 450)的分布平行,表明PenCDF与P - 450结合。PenCDF对仓鼠的诱导作用模式如先前在大鼠中报道的是3 - 甲基胆蒽型。然而,典型的酶如苯并(a)芘3 - 羟化酶和DT - 黄递酶的诱导程度比在大鼠中相对较小。在用0.5 mg/kg剂量的PenCDF预处理的仓鼠中,观察到胸腺明显萎缩和肝脏脂质过氧化物增加3倍,而体重增加完全未受抑制。这些结果表明,肝酶的诱导和胸腺萎缩可能不是PenCDF诱导仓鼠致死的直接原因。

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