JP-8 jet fuel-induced DNA damage in H4IIE rat hepatoma cells.
We investigated the genotoxicity of middle distillate jet fuel, Jet Propulsion 8 (JP-8), on H4IIE rat hepatoma cells in vitro. DNA damage was evaluated using the comet (single cell gel electrophoresis) assay. Cells were exposed for 4h to JP-8 (solubilized in ethanol (EtOH) at 0.1% (v/v)) to concentrations ranging from 1 to 20microg/ml. Exposure to JP-8 resulted in an overall increase in mean comet tail moments ranging from 0.74+/-0.065 (0.1% EtOH control) to 3.13+/-0.018,4.36+/-0.32,5.40+/-0.29,7.70+/-0.52 and 11.23+/-0.77 for JP-8 concentrations 3, 5, 10, 15 and 20microg/ml, respectively. Addition of DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (Ara-C) to cell culture with JP-8 resulted in accumulation of DNA damage strand breaks and increase in comet tail length. Inclusion of 4mM HU and 40microM Ara-C with 3, 5, 10 and 20microg/ml JP-8 concentrations resulted in increased mean tail moments to 5.94+/-0.43,10.12+/-0.72,17.03+/-0.96,and29.25+/-1.55. JP-8, in the concentrations used in this study, did not result in cytotoxicity or significant apoptosis, as measured using the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-X nick end labeling (TUNEL) assay. These results demonstrate that relevant exposures to JP-8 result in DNA damage to H4IIE cells, and suggest that DNA repair is involved in mitigating these effects.
Grant
G M
GM
George Mason University, 4400 University Drive, Fairfax, VA 22030-4444, USA.
Jackman
S M
SM
Kolanko
C J
CJ
Stenger
D A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006838:Hydrocarbons / Q000633:toxicity*; D006918:Hydroxyurea / Q000494:pharmacology; D007648:Kerosene / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D006838:Hydrocarbons; C098607:JP8 aviation fuel; D007648:Kerosene; D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; D006918:Hydroxyurea