Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells.
1,3-Butadiene, an important petrochemical, is commonly burned off when excess amounts need to be destroyed. This combustion process produces butadiene soot (BDS), which is composed of a complex mixture of polycyclic aromatic hydrocarbons in particulates ranging in size from <1 microm to 1 mm. An organic extract of BDS is both cytotoxic and genotoxic to normal human bronchial epithelial (NHBE) cells. Based on the oxidizing potential of BDS, we hypothesized that an organic extract of this particulate matter would (1) cause enzyme inactivation due to protein amino acid oxidation and (2) induce oxidative DNA damage in NHBE cells. Thus, our aims were to determine the effect of butadiene soot ethanol extract (BSEE) on both enzyme activity and the expression of proteins involved in the repair of oxidative DNA damage. Catalase was found to be sensitive to BDS as catalase activity was potently diminished in the presence of BSEE. Using Western analysis, both the alpha isoform of human 8-oxoguanine DNA glycosylase (alpha-hOGG1) and human apurinic/apyrimidinic endonuclease (APE-1) were shown to be significantly overexpressed as compared to untreated controls after exposure of NHBE cells to BSEE. Our results indicate that BSEE is capable of effectively inactivating the antioxidant enzyme catalase, presumably via oxidation of protein amino acids. The presence of oxidized biomolecules may partially explain the extranuclear fluorescence that is detected when NHBE cells are treated with an organic extract of BDS. Overexpression of both alpha-hOGG1 and APE-1 proteins following treatment of NHBE cells with BSEE suggests that this mixture causes oxidative DNA damage.
Kennedy
Christopher H
CH
Department of Biochemistry, Lake Erie College of Osteopathic Medicine, Erie, PA 16509-1025, USA. ckennedy@lecom.edu
Catallo
W James
WJ
Wilson
Vincent L
VL
Mitchell
James B
JB
D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002070:Butadienes / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D010316:Particle Size
D002070:Butadienes; D004791:Enzyme Inhibitors; D002374:Catalase; C031763:1,3-butadiene