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作为饮食中癌症化学预防剂的抗诱变剂。

Antimutagens as cancer chemopreventive agents in the diet.

作者信息

Ferguson L R

机构信息

Cancer Research Laboratory, University of Auckland Medical School, New Zealand.

出版信息

Mutat Res. 1994 May 1;307(1):395-410. doi: 10.1016/0027-5107(94)90313-1.

Abstract

It has been suggested that the use of antimutagens and anticarcinogens in everyday life will be the most effective procedure for preventing human cancer and genetic disease. There are several ways in which mutagenesis can be reduced or prevented. Chemicals which act to interfere with DNA repair or with mutagen metabolism can be effective antimutagens: however such compounds may also increase the probability of mutations by different chemicals or at different sites. In contrast, mutagen scavengers may be less prone to increase mutations by other chemicals. Selected examples illustrate that antimutagenic effects are often specific to certain classes of mutagen and/or certain test systems. Thus, if antimutagens are to have any impact on human disease, it is essential that they are specifically directed against the most common mutagens in daily life. On our current understanding, these are quite diverse in nature, so that combinations of antimutagens will probably be necessary. Two groups of mutagen scavengers (porphyrins and some types of dietary fibre) show some selectivity for large planar and hydrophobic types of carcinogen, which appear to be common in a normal Western diet. Increasing consumption of vitamins C and E, either through increased consumption of fruit and vegetables or through dietary supplementation might reduce formation of N-nitroso compounds, another common class of mutagens. Similarly, carotenoids and related compounds, already present at high quantities in some fruits and vegetables, have excellent antioxidant properties and should be able to counteract effects of endogenous metabolism and other events which generate oxidising species and free radicals. Still other types of antimutagen might be necessary to act against smaller non-planar carcinogens, but there is some question as to the importance of this type of carcinogen in a normal Western diet. It may be necessary to adjust the selection of antimutagens for different population groups, or as our understanding of mutagens in the diet develops further. Current assays for cancer chemoprevention in animals are unlikely to detect some important types of antimutagens, such as mutagen scavengers. A structured testing strategy is suggested, progressing from in vitro to in vivo antimutagenicity tests against a selected range of mutagens. Optimal use of antimutagens might be as a dietary supplement, additional to practical advice on increasing consumption of fruit and vegetables.

摘要

有人认为,在日常生活中使用抗诱变剂和抗癌剂将是预防人类癌症和遗传疾病的最有效方法。有几种方法可以减少或防止诱变。作用于干扰DNA修复或诱变剂代谢的化学物质可以是有效的抗诱变剂:然而,这类化合物也可能增加不同化学物质或在不同位点发生突变的概率。相比之下,诱变剂清除剂可能不太容易增加其他化学物质引起的突变。选定的例子表明,抗诱变作用通常对某些类别的诱变剂和/或某些测试系统具有特异性。因此,如果抗诱变剂要对人类疾病产生任何影响,至关重要的是它们要专门针对日常生活中最常见的诱变剂。根据我们目前的理解,这些诱变剂在性质上相当多样,因此可能需要抗诱变剂的组合。两组诱变剂清除剂(卟啉和某些类型的膳食纤维)对大的平面和疏水性致癌剂表现出一定的选择性,这些致癌剂在正常的西方饮食中似乎很常见。通过增加水果和蔬菜的摄入量或通过膳食补充剂增加维生素C和E的摄入量,可能会减少N-亚硝基化合物的形成,N-亚硝基化合物是另一类常见的诱变剂。同样,一些水果和蔬菜中已经大量存在的类胡萝卜素和相关化合物具有出色的抗氧化特性,应该能够抵消内源性代谢和其他产生氧化物质和自由基的事件的影响。可能还需要其他类型的抗诱变剂来对抗较小的非平面致癌剂,但这类致癌剂在正常西方饮食中的重要性存在一些疑问。可能有必要根据不同人群调整抗诱变剂的选择,或者随着我们对饮食中诱变剂的理解进一步发展而进行调整。目前用于动物癌症化学预防的检测方法不太可能检测到某些重要类型的抗诱变剂,如诱变剂清除剂。建议采用一种结构化的检测策略,从体外抗诱变性试验发展到针对选定诱变剂范围的体内抗诱变性试验。抗诱变剂的最佳用途可能是作为膳食补充剂,此外还应提供增加水果和蔬菜摄入量的实用建议。

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