The uptake and metabolism of benzo[a]pyrene from a sample food substrate in an in vitro model of digestion

Vasiluk, Luba; Pinto, Linda J.; Tsang, Wing Shan; Gobas, Frank A.P.C.; Eickhoff, Curtis; Moore, Margo M.

doi:10.1016/j.fct.2007.09.007

Cited by 25 publications

(19 citation statements)

References 52 publications

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“…This property may enable the delivery of BaP through lipid influx into the intestinal epithelium subsequent to digestion [64]. Using the Caco-2 cell model, Vasiluk et al [65] have demonstrated that uptake of B(a)P released into the gut lumen occurs through passive diffusion and its transfer into the bloodstream is aided by the fugacity gradient generated by the lipids. Additionally, works of Laurent et al [66,67] and Cavret et al [68] have shown a robust relationship between B(a)P and phenanthrene absorption and fat absorption.…”

Section: Discussionmentioning

confidence: 99%

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Diggs

Myers

Banks

et al. 2013

The Journal of Nutritional Biochemistry

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In the US alone, around 60,000 lives/year are lost due to colon cancer. Diet and environment have been implicated in the development of sporadic colon tumors. The objective of this study was to determine how dietary fat potentiates the development of colon tumors through altered B(a)P biotransformation, using the Adenomatous polyposis coli with Multiple intestinal neoplasia mouse model. Benzo(a)pyrene was administered to mice through tricaprylin, and unsaturated (USF; peanut oil) and saturated (SF; coconut oil) fats at doses of 50 and 100 μg/kg via oral gavage over a 60-day period. Blood, colon, and liver were collected at the end of exposure period. The expression of B(a)P biotransformation enzymes [cytochrome P450 (CYP)1A1, CYP1B1 and glutathione-S-transferase] in liver and colon were assayed at the level of protein, mRNA and activities. Plasma and tissue samples were analyzed by reverse phase high-performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose-dependent manner, with 100 μg/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater concentration of B(a)P metabolites, compared to the 50 μg/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen.

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Section: Discussionmentioning

confidence: 99%

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Diggs

Myers

Banks

et al. 2013

The Journal of Nutritional Biochemistry

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“…One of the best-studied PAH is benzo[a]pyrene (B[a]P), which was recently upgraded to group 1 by the IARC (IARC, in preparation). B[a]P is a hydrophobic substance that easily enters the cell by diffusion (Vasiluk et al, 2008). Within the cell it gets metabolically activated to benzo[a]pyrene diol epoxide (BPDE) by phase-1 enzymes, such as cytochrome P450 isoenzymes.…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Baumeister

Reiter

Kleinsasser

et al. 2009

European Journal of Cancer Prevention

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Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

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“…Among the different dietary items of both plant and animal origin, dietary fat is important as this component possesses a hydrophobic domain that is not disrupted easily during lipolysis [24] and facilitates the transport of PAHs, as it serves as a carrier for these lipophilic toxicants. Typical Western diet contain at least 80 g fat/day, while lipids contribute 42% of dietary energy in Western countries – 33% of it comes from dairy products [25].…”

Section: Gi Uptake Processes For Pahsmentioning

confidence: 99%

“…The food component has an infant formula comprising protein, carbohydrates and fat (3%). On the other hand, the model of Vasiluk et al [24] was conceived based on the fasting conditions in children. Skimmed milk powder (1.5% fat) was used in the food matrix.…”

Section: Models To Assess Pah Bioaccessibilitymentioning

confidence: 99%

“…The lipophilic PAHs which possess low water fugacity partition into the lipid sink of intestinal epithelial cells. The materials used as surrogates for lipid sinks are EVA [24] and C18 [68] membranes. Using a juvenile swine model, James et al [68] have demonstrated a correlation between in vivo and in vitro studies when lipid sinks were used in in vitro digestors.…”

Section: Factors That Influence Pah Bioaccessibilitymentioning

confidence: 99%

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Bioaccessibility of polycyclic aromatic hydrocarbons: relevance to toxicity and carcinogenesis

Harris

Banks

Mantey

et al. 2013

Expert Opinion on Drug Metabolism & Toxicology

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Introduction Bioaccessibility is a growing area of research in the field of risk assessment. As polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants, they are the toxicants of focus to establish cancer risks in humans. Orally ingested PAHs also cause toxicity and even affect the pharmacokinetic behavior of some therapeutic agents. Toward this end, bioaccessibility is being used as a tool to assess the risk of PAHs via dietary exposures. Areas covered This review covers some in vitro bioaccessibility models for PAHs that have been used for the past one-and-a-half decade. This review also considers the factors that influence bioaccessibility and debates the merits and limitations of using a bioaccessibility concept for estimating risk from ingestion of PAH-contaminated soil and food. Finally, the authors discuss the implications of bioaccessibility for PAH-induced toxicity and cancers in the context of risk assessment. Expert opinion So far, much of the focus on PAH bioaccessibility is centered on soil as a preferential matrix. However, ingestion of PAHs through diet far exceeds the amount accidentally ingested through soil. Therefore, bioaccessibility could be exploited as a tool to assess the relative risk of various dietary ingredients tainted with PAHs. While bioaccessibility is a promising approach for assessing PAH risk arising from various types of contaminated soils, none of the models proposed appears to be valid. Bioaccessibility values, derived from in vitro studies, still require validation from in vivo studies.

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The uptake and metabolism of benzo[a]pyrene from a sample food substrate in an in vitro model of digestion

Cited by 25 publications

References 52 publications

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Bioaccessibility of polycyclic aromatic hydrocarbons: relevance to toxicity and carcinogenesis

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