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肝脏肿瘤促进剂1,4-双[2-(3,5-二氯吡啶氧基)]苯对小鼠和大鼠肝脏影响的生化特性研究

Biochemical characterization of the hepatic effects in mice and rats of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a hepatic neoplasm promoter.

作者信息

Romano M, Esteve A, Coccia P, Masturzo P, Galliani G, Ghezzi P, Salmona M

出版信息

Toxicol Appl Pharmacol. 1986 Apr;83(2):379-85. doi: 10.1016/0041-008x(86)90314-5.

Abstract

The biochemical effects on the liver of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), a phenobarbital-like enzyme inducer, were studied in the mouse and rat. In mice a single dose of TCPOBOP (3 mg/kg, ip) caused marked and long-lasting (at least 7 days) induction of liver cytochrome P-450, 7-ethoxycoumarin-O-deethylase, and epoxide hydrolase. TCPOBOP had much less effect in rats than in mice, even at a higher dose (30 mg/kg) TCPOBOP also induced DNA synthesis in mice and rats but ornithine decarboxylase activity only in mice. In addition, in mice but not in rats, TCPOBOP increased microsomal membrane fluidity, as detected by fluorescence polarization measurements.

摘要

研究了1,4-双[2-(3,5-二氯吡啶氧基)]苯(TCPOBOP),一种类似苯巴比妥的酶诱导剂,对小鼠和大鼠肝脏的生化影响。在小鼠中,单剂量的TCPOBOP(3mg/kg,腹腔注射)可引起肝脏细胞色素P-450、7-乙氧基香豆素-O-脱乙基酶和环氧化物水解酶的显著且持久(至少7天)的诱导。TCPOBOP对大鼠的作用远小于对小鼠的作用,即使在更高剂量(30mg/kg)时也是如此。TCPOBOP还诱导小鼠和大鼠的DNA合成,但仅在小鼠中诱导鸟氨酸脱羧酶活性。此外,通过荧光偏振测量检测发现,TCPOBOP增加了小鼠而非大鼠的微粒体膜流动性。

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