RELATIONSHIP BETWEEN DIETARY FAT TYPE AND METABOLIC FATE OF FLUORANTHENE IN F-344 RATS

Abstract

Harmful health effects such as toxicity and cancer to humans may be attributed to consumption of fatty foods contaminated with environmental toxicants. The objective of this study was to delineate the effect of dietary fat on disposition; metabolism and DNA adduct formation of fluoranthene (FLA). Fluoranthene was administered to 10-week old F-344 male rats in unsaturated (olive oil) and saturated (palm kernel oil) fats at doses of 50 and 100 μg/kg via oral gavage. Blood, target tissues, urine and feces were collected at various time points post-FLA exposure. Samples were subjected to liquid-liquid extraction and analyzed by reverse-phase HPLC equipped with a fluorescence detector for detection and quantitation of FLA metabolites. DNA was isolated from the tissues of FLA-exposed rats, subjected to 32P-post labeling and resolved by thin layer chromatography to measure FLA-DNA adducts. An increase in FLA metabolite concentrations was observed in target tissues in the saturated fat treatment group compared with the unsaturated fat group. The FLA-DNA adduct concentrations were high in tissues of rats that received FLA through saturated fat. The concentration of FLA metabolites and DNA adducts showed a dose-dependent increase that was statistically significant (P < 0.005) for saturated fat. These findings demonstrate that the high residence time of FLA in saturated fat contributes reactive metabolites of FLA that bind with DNA and cause damage to target organs.