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慢性口服给药期间2-乙酰氨基芴在BAlB/c和C57Bl/6小鼠体内的组织结合情况。

Tissue binding of 2-acetylaminofluorene in BAlB/c and C57Bl/6 mice during chronic oral administration.

作者信息

Jackson C D, Weis C, Shellenberger T E

出版信息

Chem Biol Interact. 1980 Oct;32(1-2):63-81. doi: 10.1016/0009-2797(80)90068-x.

Abstract

Blood and tissue binding levels of [9-14C]2-acetylaminofluorene ([9-14C]2-AAF) administered in the diets of female BALB/c and C57Bl/6 mice, were determined. Blood and liver levels reached a plateau after 2--4 weeks, while levels in bladder tissue continued to increase. Binding levels two weeks administration were determined in liver, bladder, kidney, lung, spleen, heart and skeletal muscle. In every instance the binding was linear over a dose range of 0.5--500 ppm 2-AAF. Removal of the 2-AAF in the diet after 48 weeks resulted in a rapid loss of radioactivity from blood and liver, with little or no loss from bladder tissue. The linear dose-response relationship of tissue binding correlated well with the previously reported linear dose response curve for liver tumors but did not correlated with the reported non-linear dose response curve for bladder tumors. A reversed correlation was found in the ability of the tissue to remove bound fluorene residues and the observed rate of tumor occurrence following discontinued administration of the carcinogen.

摘要

测定了给予雌性BALB/c和C57Bl/6小鼠含[9-¹⁴C]2-乙酰氨基芴([9-¹⁴C]2-AAF)的饮食后,其血液和组织中的结合水平。血液和肝脏水平在2至4周后达到平台期,而膀胱组织中的水平持续升高。在给药两周后测定了肝脏、膀胱、肾脏、肺、脾脏、心脏和骨骼肌中的结合水平。在每种情况下,在0.5至500 ppm 2-AAF的剂量范围内,结合呈线性关系。48周后从饮食中去除2-AAF导致血液和肝脏中的放射性迅速丧失,而膀胱组织中几乎没有丧失。组织结合的线性剂量反应关系与先前报道的肝脏肿瘤线性剂量反应曲线密切相关,但与报道的膀胱肿瘤非线性剂量反应曲线不相关。在停止给予致癌物后,发现组织去除结合芴残基的能力与观察到的肿瘤发生率呈反向相关。

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