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替代致癌性生物测定法进行毒性预测的方法:我们做到了吗?

Alternatives to the carcinogenicity bioassay for toxicity prediction: are we there yet?

机构信息

Environment and Health Department, Istituto Superiore di Sanita, Viale Regina Elena 299 00161, Rome, Italy.

出版信息

Expert Opin Drug Metab Toxicol. 2012 Apr;8(4):407-17. doi: 10.1517/17425255.2012.666238. Epub 2012 Feb 23.

Abstract

INTRODUCTION

For decades, traditional toxicology has been the ultimate source of information on the carcinogenic potential of chemicals; however, with increasing demand on regulation of chemicals and decreasing resources for testing, opportunities to accept 'alternative' approaches have dramatically expanded. The need for tools able to identify carcinogens in shorter times and at a lower cost in terms of animal lives and money is still an open issue, and the present strategies and regulations for carcinogenicity prescreening do not adequately protect human health.

AREAS COVERED

This paper briefly summarizes the theories on the early steps of carcinogenesis and presents alternative detection methods for carcinogens based on genetic toxicology, structure-activity relationships and cell transformation assays.

EXPERT OPINION

There is evidence that the combination of Salmonella and structural alerts for the DNA-reactive carcinogens, and in vitro cell transformation assays for nongenotoxic carcinogens, permits the identification of a very large proportion of carcinogens. If implemented, this alternative strategy could improve considerably the protection of human health.

摘要

简介

几十年来,传统毒理学一直是化学物质致癌潜力信息的最终来源;然而,随着对化学品监管的需求增加,以及用于测试的资源减少,接受“替代”方法的机会大大增加。在更短的时间内、以更少的动物生命和资金成本来识别致癌物的工具仍然是一个悬而未决的问题,并且目前用于致癌性预筛选的策略和法规不能充分保护人类健康。

涵盖领域

本文简要总结了致癌作用早期步骤的理论,并提出了基于遗传毒理学、结构-活性关系和细胞转化试验的致癌物替代检测方法。

专家意见

有证据表明,将沙门氏菌与 DNA 反应性致癌物的结构警报以及非遗传毒性致癌物的体外细胞转化试验相结合,可以鉴定出很大一部分致癌物。如果实施这种替代策略,可以大大改善对人类健康的保护。

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