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

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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.