Mechanism of DNA damaging by photo- and metabolic products of carcinogenic ethylbenzene

致癌乙苯的光和代谢产物损伤 DNA 的机制

基本信息

批准号：
16590097
负责人：
KOJIMA Nakao
金额：
$ 1.86万
依托单位：
Meijo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Ethylbenzene is an air pollutant detected often in the environment. Ethylbenzene is a non-mutagenic carcinogen and its carcinogenesis mechanism is not elucidated. In this research, we showed that ethylbenzene transformed into genotoxic by light exposure or metabolism. Its underlying mechanism involves peroxiethylbenzene and ethyl catechol/hydroquinone, which generates reactive oxygen species in their redox reaction with Cu and damages DNA especially at 5' of consecutive guanine. We expanded this mechanism to other several environmental chemicals that follows. 1)Nonylphenol, a government-certified endocrine disruptor turned to be genotoxic by light irradiation. 2)Methyl paraben, a widely used preservative, was activated by the combination of light and metabolism. 3)An additional functional group suppressed DNA damage of catechol. This structure-activity relationship is useful to predict the risk of chemicals. The key structure for DNA damaging activity is aromatic hydroxylation and this is important for other activities such as endocrine disruption. 4)Plasticizers revealed its potential estrogenic activity after sunlight exposure. 5)Sunscreens generated hydroxyl radical and activated themselves by sunlight irradiation. 6)A specific hydroxylation made flavonoides highly anti-estrogenic. As stated above, this study provided many important findings for risk assessment of environmental chemicals.

乙烯苯是一种在环境中经常检测到的空气污染物。乙烯苯是一种非毒素致癌，其癌变机制未阐明。在这项研究中，我们表明乙烯通过光暴露或代谢转化为遗传毒性。其潜在机制涉及过氧乙基苯苯和儿茶酚/氢喹酮，它们在氧化还原反应中产生活性氧，并损害DNA，尤其是在连续的鸟嘌呤的5'时。我们将此机制扩展到随后的其他几种环境化学物质。 1）Nonylphenol，由政府认证的内分泌破坏者通过光照射变为遗传毒性。 2）羟基苯甲酸酯是一种广泛使用的防腐剂，通过光和代谢的组合激活。 3）另一个功能组抑制了儿茶酚的DNA损伤。这种结构活性关系对于预测化学物质的风险很有用。 DNA损伤活性的关键结构是芳族羟基化，这对于其他活性（例如内分泌破坏）很重要。 4）增塑剂揭示了阳光暴露后其潜在的雌激素活性。 5）防晒霜产生了羟基自由基，并通过阳光照射激活了自己。 6）特定的羟基化制造的黄酮剂高度抗雌激素。如上所述，这项研究为环境化学品的风险评估提供了许多重要的发现。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Formation of DNA damaging product from light-irradiated nonylphenol

光照射壬基酚形成 DNA 损伤产物

DOI：
发表时间：
2005
期刊：
J.Health Sci. 52(1)
影响因子：
0
作者：
今井輝子;井本真澄;坂本久恵;橋本満;Michiru Ida;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Yasuyuki Fujiwara;Toshiyuki Kaji;Toshiyuki Kaji;Tatsuya Funahashi;Tatsuya Funahashi;Tatsuya Funahashi;Ito et al.;Okamoto et al.;Okamoto et al.;植田康次;Okamoto et al.
通讯作者：
Okamoto et al.

Activation of chemicals in the environment.

环境中化学物质的活化。

DOI：
发表时间：
2006
期刊：
Bul.Res.Inst.(Meijo Univ.) 11 (in press)
影响因子：
0
作者：
H.Nakagawa;M.Takusagawa;H.Arima.;K.Furukawa;T.Ozawa;N.Ikota;et al.;Kojima
通讯作者：
Kojima

Formation of estrogenic products from environmental phthalate esters under light exposure.

环境邻苯二甲酸酯在光照下形成雌激素产物。

DOI：
发表时间：
2006
期刊：
Chemosphere (in press)
影响因子：
0
作者：
今井輝子;井本真澄;坂本久恵;橋本満;Michiru Ida;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Yasuyuki Fujiwara;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Chika Yamamoto;Yasuyuki Fujiwara;Toshiyuki Kaji;Toshiyuki Kaji;Tatsuya Funahashi;Tatsuya Funahashi;Tatsuya Funahashi;Ito et al.;Okamoto et al.
通讯作者：
Okamoto et al.

Isoflavonoids with antiestrogenic activity from Millettia pachycarpa