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主流和侧流香烟烟雾冷凝物在小鼠组织和人体皮肤中诱导产生的总DNA加合物水平的比较。

Comparison of total DNA adduct levels induced in mouse tissues and human skin by mainstream and sidestream cigarette smoke condensates.

作者信息

Carmichael P L, Hewer A, Jacob J, Grimmer G, Phillips D H

机构信息

Haddow Laboratories, Institute of Cancer Research, Sutton, UK.

出版信息

IARC Sci Publ. 1993(124):321-6.

PMID:8225501
Abstract

Cigarette smoke condensates (CSCs) of both mainstream (MS) and sidestream (SS) smoke were used to treat mice topically in equivalent amounts. Human skin maintained in short-term culture was also treated with the condensates. DNA adducts, induced by the CSCs and detected by the nuclease P1 method of 32P-postlabelling, were quantified in a number of murine tissues and in the human skin DNA. In the five mouse tissues studied both MS-CSC and SS-CSC produced characteristic diagonal radioactive zones on TLC, indicative of the formation of multiple DNA adducts. In three tissues (skin, lung and kidney), SS-CSC induced greater total adduct levels than MS-CSC (statistically significant in skin and kidney, p < 0.05). However, greater adduct levels induced by MS-CSC were recorded for heart and bladder DNA (not statistically significant). Similar results to those found in mouse skin were obtained with human skin; SS-CSC induced a approximately 2-fold greater level of DNA adducts than MS-CSC (p < 0.05). Incubation of DNA directly with condensates in vitro demonstrated that DNA adducts could be formed without an exogenous metabolizing system. This direct interaction of condensates with DNA occurred at similar levels for both MS- and SS-CSC, although inclusion of an oxygen radical-generating system enhanced the SS-CSC binding to a greater extent than that of the MS-CSC.

摘要

将主流(MS)烟雾和侧流(SS)烟雾的香烟烟雾冷凝物(CSC)等量局部用于处理小鼠。短期培养的人皮肤也用这些冷凝物进行处理。通过32P后标记的核酸酶P1方法检测由CSC诱导的DNA加合物,并在多种小鼠组织和人皮肤DNA中进行定量。在所研究的五种小鼠组织中,MS-CSC和SS-CSC在薄层层析(TLC)上均产生特征性的对角放射性区域,表明形成了多种DNA加合物。在三种组织(皮肤、肺和肾)中,SS-CSC诱导的总加合物水平高于MS-CSC(在皮肤和肾中具有统计学意义,p<0.05)。然而,MS-CSC诱导的心脏和膀胱DNA加合物水平更高(无统计学意义)。在人皮肤中获得了与小鼠皮肤相似的结果;SS-CSC诱导的DNA加合物水平比MS-CSC高约2倍(p<0.05)。体外将DNA直接与冷凝物孵育表明,无需外源性代谢系统即可形成DNA加合物。冷凝物与DNA的这种直接相互作用在MS-CSC和SS-CSC中发生的水平相似,尽管加入产生活性氧的系统后,SS-CSC与DNA的结合增强程度比MS-CSC更大。

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