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.

Inter-species comparison of liver and small intestinal microsomal metabolism of fluoranthene.

The magnitude of susceptibility to toxicant exposure may depend on the ability of animals to metabolize the chemicals. The present study has been undertaken to see whether any differences exist among mammals in the metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon (PAH) compound. Microsomes were isolated from the small intestine and liver of rat, mouse, hamster, goat, sheep, pig, dog, cow, monkey, and humans (commercially procured), and incubated with FLA. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA/metabolites by reverse-phase HPLC with fluorescence detection. The metabolism of FLA in both liver and small intestine was in the order: human > monkey > cow > goat > sheep > dog > pig > hamster > rat > mouse under conditions of the test system used. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in intestine in all the species studied. The FLA metabolites identified were FLA 2,3-diol, trans-2,3-dihydroxy-1,10b-epoxy-1,2,3,10beta tetrahydro FLA (2,3D FLA), 3-hydroxy FLA, and 8-hydroxy FLA. The rodent microsomes produced considerably higher proportion of FLA 2,3-diol, and 2,3D FLA than did pig, dog, and humans. On the other hand, microsomes from higher mammals converted a greater proportion of FLA to 3-hydroxy FLA, the detoxification product of FLA. Overall, our results revealed a great variation among species to metabolize FLA.

Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are ubiquitous in the environment. These contaminants generate considerable interest, because some of them are highly carcinogenic in laboratory animals and have been implicated in breast, lung, and colon cancers in humans. These chemicals commonly enter the human body through inhalation of cigarette smoke or consumption of contaminated food. Of these two pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs have been published, factors affecting the accumulation of PAHs in the diet, their absorption following ingestion, and strategies to assess risk from exposure to these hydrocarbons following ingestion have received much less attention. This review, therefore, focuses on concentrations of PAHs in widely consumed dietary ingredients along with gastrointestinal absorption rates in humans. Metabolism and bioavailability of PAHs in animal models and the processes, which influence the disposition of these chemicals, are discussed. The utilitarian value of structure and metabolism in predicting PAH toxicity and carcinogenesis is also emphasized. Finally, based on intake, disposition, and tumorigenesis data, the exposure risk to PAHs from diet, and contaminated soil is presented. This information is expected to provide a framework for refinements in risk assessment of PAHs from a multimedia exposure perspective.