Environmental metabolite, 1,2-diacetylbenzene, produces cytotoxicity through ROS generation in HUVEC cells.
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.
Kim
Min Kyeong
MK
Department of Biochemistry and Molecular Biology, Yeungnam University, Daegu, Republic of Korea.
Kim
Kwang Seok
KS
Chung
Jae Heun
JH
Kim
Jung Hye
JH
Kim
Jae-Ryong
JR
Chung
Hae Young
HY
Kim
Min-Sun
MS
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
D000098:Acetophenones; D017382:Reactive Oxygen Species; D012997:Solvents; C048792:1,2-diacetylbenzene