JP-8 jet fuel-induced DNA damage in H4IIE rat hepatoma cells

We investigated the genotoxicity of middle distillate jet fuel, Jet Propuls ion 8 (JP-X), on H4IIE rat hepatoma cells in vitro. DNA damage was evaluate d using the comet (single cell gel electrophoresis) assay. Cells were expos ed for 4 h to JP-8 (solubilized in ethanol (EtOH) at 0.1% (v/v)) to concent rations ranging from 1 to 20 mug/ml. Exposure to JP-8 resulted in an overal l increase in mean comet tail moments ranging from 0.74 +/- 0.065 (0.1% EtO H control) to 3.13 +/- 0.018, 4.36 +/- 0.32, 5.40 +/- 0.29. 7.70 +/- 0.52 a nd 11.23 +/- 0.77 for JP-8 concentrations 3, 5, 10, 15 and 20 mug/ml, respe ctively. Addition of DNA repair inhibitors hydroxyurea (HU) and cytosine ar abinoside (Ara-C) to cell culture with JP-8 resulted in accumulation of DNA damage strand breaks and increase in comet tail length. Inclusion of 4 mM HU and 40 muM Ara-C with 3, 5, 10 and 20 mug/ml JP-8 concentrations resulte d in increased mean tail moments to 5.94+/-0.43, 10.12+/-0.72, 17.03+/-0.96 , and 29.35+/- 1.55. JP-8, in the concentrations used in this study, did no t result in cytotoxicity or significant apoptosis, as measured using the te rminal deoxynucleotidyl transferase (TDT)-mediated dUTP-X nick end labeling (TUNEL) assay. These results demonstrate that relevant exposures to JP-8 r esult in DNA damage to H4IIE cells, and suggest that DNA repair is involved in mitigating these effects. (C) 2001 Published by Elsevier Science B.V.