Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation.

Once ingested, dioxins and dioxin-like compounds are excreted extremely slowly. Excretion can be evaluated by its half-life. Half-lives estimated from observed concentrations are affected by excretion and ongoing exposure. We investigated the change in apparent half-life using a theoretical model based on exposure to dioxin and dioxin-like compounds. We carried out longitudinal measurements of the blood concentration of dioxins and dioxin-like compounds in a Yusho cohort during 2002 to 2010. We estimated the change in decay rates of 2,3,4,7,8-PeCDF and octachlorodibenzodioxin (OCDD) using a second-order equation. We found that the decay rate of OCDD increased, whereas the decay rate of 2,3,4,7,8-PeCDF of patients with a relatively high concentration of 2,3,4,7,8-PeCDF decreased. OCDD results were in accordance with decreasing levels of dioxin and dioxin-like compounds in the environment. The decay rate of OCDD in the body was affected by the decay rate of OCDD in the environment by ingestion because it was near the steady-state. In contrast, the decay rate of 2,3,4,7,8-PeCDF in the body was affected less by ingestion from the environment because it was far higher than in the steady-state. We demonstrated that the level of 2,3,4,7,8-PeCDF in the environment is decreasing. The excretion half-life is longer than the environmental half-life, thus the excretion half-life in a Yusho patient is increased.