In vitro genotoxicity investigations of jet fuel

Abstract

The 60 billion gallons of jet propulsion fuels consumed worldwide create an exposure situation to over two million military and civilian personnel per year. The potential mutagenic, genotoxic and cytotoxic potency of military jet fuel was investigated in this study through in vitro systems such as human peripheral lymphocytes and metabolically competent hepatic cell lines. A battery of genotoxicological evaluations is employed, focusing on the comet assay to examine the induction of DNA damage. Cellular exposures to fuel were carried out directly and indirectly with an ethanol (EtOH) carrier. The fuel was found to be nonmutagenic with and without metabolic activation in the Salmonella microsomal mutagenicity assay. Chromosomal aberrations were apparent through a slight but not significant increase in sister chromatid exchanges in peripheral lymphocytes directly exposed to the fuel. DNA damage was induced as a result of fuel exposure as measured by the comet assay in peripheral lymphocytes and cell lines investigated. DNA damage increases with increasing exposure to the fuels and the activation of repair processes was demonstrated. There was no evidence of the formation of bulky aromatic adducts from fuel exposure investigated through P 32-postlabeling. However, evaluations of a fuel exposed hepatic cell line via oxidative comet assay showed an increase in DNA damage implying that oxidative mechanism have a role in the genotoxic effects of the fuel. The in vitro evidence of cytotoxic and genotoxic insult as a result of jet fuel exposure presented here, suggest a reevaluation of the fuel components and exposure limits. Table XV Mean tail moment measures for JP-8 indirectly exposed (0.1% EtOH (v/v)) H4IIE cells analyzed by the FLARE™ assay for oxidative DNA damage………………………………………………….……………..88 REVIEW OF LITERATURE 1. Fuel Introduction Petroleum middle distillates (PMDs) are the broad classification of fuels, which include kerosene, diesel fuel, home heating oil, and jet fuel with and without additives. The exact composition of PMDs varies but all include linear and branched chain aliphatics, cycloparaffins, and aromatics in the C 10-C 20 range. Jet fuels are produced in part from the distillation of crude oil at atmospheric pressure classifying them as straight run middle distillate kerosene cuts (Nessel et al., 1999). The adverse effects of human exposure to these fuels are of growing concern due to their extensive use throughout the military and the civilian aviation industry. PMDs have been shown to cause chronic irritation and inflammation in animals and humans, but are only slightly irritating to the eyes (Broddle et al., 1996, Upreti et al., 1989, Nessel et al., 1999). Exposures to PMDs have shown altered histology including a compromised hematologic profile, decreased organ weights as well as liver, spleen, thymus, kidney, adrenal, and lymph node lesions in mice (Broddle et al., 1996, Upreti et al., 1989). Rats exposed interperitonealy to petroleum, demonstrated hepatoxicity by an increase in liver alkaline ph...