報告書番号

V06004

タイトル（和文）

哺乳動物に対する化学物質の毒性発現メカニズムに関する調査研究

タイトル（英文）

Current review and perspective of the studies on mechanism of toxicities of harmful chemicals against mammals.

概要 （図表や脚注は「報告書全文」に掲載しております）

多くの化学物質が産業活動に伴い環境中に放出され、それらの一部は人体や野生生物に対して有害な作用を持つことが明らかにされている。今回われわれは、今後の研究課題を抽出する目的で、化学物質による毒性発現メカニズムの研究に関して動向調査を行い、時系列でその推移を明らかにした。また調査結果に基づき、今後の研究課題として以下の三つを提示した。①従来の方法に代わる一過性の遺伝子操作による迅速な責任遺伝子の決定、②責任遺伝子を利用した有害性化学物質の無害化、排出手法の確立、③種間差を考慮した健康リスク評価手法の確立。

概要 （英文）

Numerous chemical compounds have been utilized in our industry and agriculture, and some of these are emitted to our environment. Parts of these chemicals are potentially harmful and could be persistent pollutants for the ecological system. The authors reviewed the current issues of the mechanistic studies on the toxicity of the harmful compounds against mammals, and showed the possible future subjects in this field.
Numbers of studies have focused on the harmful effects of the emitted pollutants for the human and other mammals. The strategies of these studies have much variety, and have been changing depend on the technical advance. We searched the trends of "in vivo" and "in vitro" mechanistic studies separately. Biggest part of the mechanistic studies was the observation of changes in molecular status such as quantity, translocation, modification, structure and function, to which physiological endpoints could be attributed. this type of study has been constantly carried out from late 80's in vivo and early 90's in vitro respectively. The next biggest portion of the mechanistic studies was determination of genes or proteins involved in the toxicity of chemical compounds. from late 90's, based on the techniques of gene manipulation (knockout and transgenic strategies), researchs on the genetic mechanism of toxicity of the harmful chemicals both in vivo and in vitro have been vigorously carried out. These studies have revealed the critical responsible genes for the toxicity, accumulation, detoxification and excretion of several harmful compounds. Elucidation of the mechanism of toxicity on the genetic basis could be one of the major stream among this field. Based on these survey, we figured out and discussed about the three possible future subjects in this field; first: rapid determination of responsible genes using transient gene delivery by viral or lippoplex vector in vivo, that is alternatives of conventional gene manipulation methods, second: gene therapy for the wildlife or human, that could resolve the toxicity and accelerate excretion of harmful chemicals, third: reliable risk assessment of chemical compounds considering interspecies or individual differences.

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