Seoul National University, Korea
Jin-Ho Chung received his Ph.D. from the Johns Hopkins University School of Public Health. He has been Professor of College of Pharmacy at Seoul National University (SNU). Jin-Ho Chung manages an organization as director at Institute of Environment Protection and Safety of SNU since June 2008. In Jan. 2009, he served also as President of Korean Society of Toxicology. He served and serves in numerous advisory functions in different national organizations. He has contributed to the scientific achievements with a significant number of publications in major journals
Arsenic is a ubiquitous heavy metal in various environmental media that include soil, air, and water. Numerous epidemiological studies have reported a close relationship between arsenic and skin carcinogenic effects. In addition, arsenic was also known as a blister agent in skin, and thus its derivatives have been used as a chemical weapon. However, the mechanism of blister formation, one of the most important targets for arsenic toxicity, remains poorly understood. Here we found that arsenic could induce cytotoxicity and inflammation in keratinocyte, which play key roles in the formation of blister. In this study, we used arsenic (AsIII) and trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMAIII), which has been found highly reactive and toxic in various cells. Treatment of AsIII and MMAIII resulted in significant reduction of viability of keratinocyte (HaCaT) in a concentration- and time-dependent manner. Cell death forms, which are apoptosis and necrosis, are occurring simultaneously in AsIII and MMAIII. These cell death were found to be mediated by the reactive oxygen species (ROS), depletion of glutathione by AsIII and MMAIII. Consistent with these findings, mitochondrial membrane potential disruption, caspase-3 activation and DNA fragmentation were observed by treatments with AsIII and MMAIII, as determined by fluorescence microscopy and flow cytometry. Exposure to arsenicals also stimulated secretion of pro-inflammatory cytokine in keratinocytes, resulting in increased levels of TNF-α, IL-1α, and IL-6. In summary, this study provides an important evidence for the role of AsIII and MMAIII in arsenic-associated cytotoxicity and inflammation response in keratinocytes, suggesting a new solution to inhibit the toxicant-induced blister formation.