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某些氨基甲酸酯类化合物作为多组织姐妹染色单体交换诱导剂的效能及其与已知致癌活性的比较。

Potency of some carbamates as multiple tissue sister chromatid exchange inducers and comparison with known carcinogenic activities.

作者信息

Cheng M, Conner M K, Alarie Y

出版信息

Cancer Res. 1981 Nov;41(11 Pt 1):4489-92.

PMID:7306972
Abstract

The ethyl, ethyl N-hydroxy, isopropyl, and methyl esters of carbamic acid were examined for their abilities to induce sister chromatid exchanges (SCEs) in alveolar macrophages, bone marrow, and regenerating liver cells of C57BL/6J X DBA/2J F1 mice. The relative potencies in inducing SCE, ethyl greater than ethyl N-hydroxy- greater than isopropyl, paralleled previously described activities for induction of lung adenomas in strain A mice. The noncarcinogenic methyl carbamate was inactive in the SCE assay. Relative to bone marrow, regenerating liver and alveolar macrophage cells demonstrated increased susceptibility to carbamate-induced SCE. Of all carbamates studied, only the directly active compound, ethyl N-hydroxycarbamate, produced distinctly different responses in extrahepatic tissues of hepatectomized and intact mice. In intact mice, SCE levels induced by ethyl carbamate in bone marrow and alveolar macrophage cells were not significantly different whether assay followed the last of 12 (three times weekly) serial injections of 2.2 mmol/kg each or after a single injection of 2.2 mmol/kg. Linear regression relationships of log ethyl carbamate versus log SCE or log adenoma response were found to be parallel with the two assays having similar sensitivities.

摘要

研究了氨基甲酸乙酯、N-羟基氨基甲酸乙酯、异丙酯和甲酯在C57BL/6J×DBA/2J F1小鼠的肺泡巨噬细胞、骨髓和再生肝细胞中诱导姐妹染色单体交换(SCE)的能力。诱导SCE的相对效力为:乙酯>N-羟基乙酯>异丙酯,这与先前描述的在A系小鼠中诱导肺腺瘤的活性相似。非致癌性的氨基甲酸甲酯在SCE试验中无活性。相对于骨髓,再生肝和肺泡巨噬细胞对氨基甲酸酯诱导的SCE表现出更高的敏感性。在所有研究的氨基甲酸酯中,只有直接具有活性的化合物N-羟基氨基甲酸乙酯在肝切除小鼠和完整小鼠的肝外组织中产生了明显不同的反应。在完整小鼠中,无论是在每周三次连续注射12次、每次2.2 mmol/kg(末次注射后进行检测),还是在单次注射2.2 mmol/kg后进行检测,氨基甲酸乙酯在骨髓和肺泡巨噬细胞中诱导的SCE水平均无显著差异。发现氨基甲酸乙酯的对数与SCE对数或腺瘤反应对数之间的线性回归关系是平行的,两种检测方法具有相似的敏感性。

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