title: Environmental metabolite, 1,2-diacetylbenzene, produces cytotoxicity through ROS generation in HUVEC cells.
abstract: Organic solvents are ubiquitous in industrial and household surroundings, and thus individuals are easily exposed. 1,2-Diethylbenzene (DEB) is one of organic solvents contained in gasoline or jet fuels. DEB is absorbed by dermal or inhalation routes, metabolized by cytochrome P-450 in the liver, and ultimately affects mammalian functions. 1,2-Diacetylbenzene (1,2-DAB), which is a putative metabolite of 1,2-DEB, resulted in neuropathological effects on rodent central and peripheral nervous systems. To elucidate the possibility of 1,2-DAB effects on the vascular system, studies were undertaken to examine whether 1,2-DAB induces endothelial cytotoxicity through reactive oxygen species (ROS) generation. Incubation of human umbilical vein endothelial cells (HUVEC) with lower concentrations (4 or 8 microM) of 1,2-DAB induced inhibition of cellular growth and at higher amounts (16 or 32 microM) produced apoptosis. Endothelial cells cultured with 1,2-DAB also showed increased intracellular ROS production and morphological alterations indicative of senescence. Pretreatment with the well-known antioxidant glutathione or N-acetylcysteine (NAC) reduced cytotoxicity induced by 1,2-DAB. Taken together, the results provide evidence that cytotoxicity induced by 1,2-DAB in endothelial cells may be mediated by ROS generation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Kim
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Chung
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000098:Acetophenones / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012997:Solvents / Q000633:toxicity*; D014471:Umbilical Veins / Q000187:drug effects
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; D012997:Solvents; C048792:1,2-diacetylbenzene