Effect of dietary fat on metabolism and DNA adduct formation after acute oral exposure of F-344 rats to fluoranthene.
Adverse health effects such as cancer and toxicity may be attributed to consumption of chemically contaminated food rich in fat. This leads to a larger intake and retention of lipophilic toxic chemicals in the body with an increase in risks to human health. The objective of this study was to characterize the effect of dietary fat on disposition and metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon compound. FLA was administered to F-344 rats in monounsaturated (peanut oil), polyunsaturated (corn oil) and saturated (coconut oil) fats at doses of 50 and 100 microg/kg via oral gavage. Blood, small intestine, liver, lung, testis, adipose tissue, urine and feces were collected at various time points' post-FLA exposure. Samples were analyzed by reverse-phase high-performance liquid chromatography for FLA parent compound and metabolites. DNA was isolated from the tissues and subjected to (32)P-post labeling to measure FLA-DNA adducts. The concentrations of unchanged FLA (FLA parent compound) and its metabolites showed an increase for the saturated fat treatment group compared with mono- and polyunsaturated fat groups. The FLA-DNA adduct concentrations were high in tissues of rats that received FLA through saturated fat. The toxicokinetic parameters, concentrations of FLA metabolites and FLA-DNA adduct showed a dose-dependent increase, and this increase was statistically significant (P<.05) for saturated fat. These findings clearly demonstrate that the high residence time of FLA parent compound in saturated fat allows extensive metabolism, contributing reactive metabolites of FLA that bind with DNA and causing marked damage in a long-term exposure scenario.
Walker
Stormy A
SA
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Addai
Amma B
AB
Mathis
Malcolm
M
Ramesh
Aramandla
A
D000818:Animals; D018736:DNA Adducts / Q000096:biosynthesis*; D004041:Dietary Fats / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D005449:Fluorenes / Q000378:metabolism* / Q000493:pharmacokinetics*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D018736:DNA Adducts; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005449:Fluorenes; C007738:fluoranthene