Dose-dependent benzo(a)pyrene [B(a)P]–DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P

Ramesh, Aramandla; Knuckles, Maurice E.

doi:10.1016/j.canlet.2005.09.016

Cited by 30 publications

(16 citation statements)

References 36 publications

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“…Overall, the B(a)P metabolite types identified in our study are in agreement with published literature [55,72–75] which documented that orally administered B(a)P undergoes extensive biotransformation producing an array of metabolites and the concentrations of these metabolites were B(a)P dose-dependent. The relatively high concentrations of B(a)P diols and quinones in plasma and colon of mice that ingested B(a)P through saturated fat compared to unsaturated fat suggest that B(a)P incorporated through saturated fat is likely to generate more toxic metabolites.…”

Section: Discussionsupporting

confidence: 91%

“…The preponderance of deoxyguanosine (dG) adducts relative to that of dA adducts are consistent with the results of studies reported from our laboratory [72] and those of others [83,85]. Since the carcinogenicity of B(a)P results from this toxicant's propensity to form dG adducts [86], the greater incidence of these adducts at 100 μg/kg, compared to 50 μg/kg, seen in the present study, indicate the vulnerability of tissues to damage resulting from long term exposure to high doses of B(a)P through dietary fat.…”

Section: Discussionsupporting

confidence: 91%

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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: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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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“…Mice that were treated with50 B(a)P/kg bw+ olive oil had lower concentration of metabolites in the plasma, colon and liver compared to their counterparts treated with 50 μg B(a)P/kg bw alone. The metabolite types that were identified in our study are in agreement with previous studies conducted which concluded that orally administered B(a)P goes through an extensive biotransformation generating an array of metabolites [75]. Mice that were treated with 50 μg B(a)P/kg bw only displayed a greater amount of reactive metabolites such as B(a)P 7,8 diol; 3,6-and 6,12-B(a)P diones compared to mice treated with 50 μg B(a)P/kg bw + olive oil that had a smaller percentage of these metabolites.…”

Section: 0 Discussionsupporting

confidence: 92%

Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model

Banks

Amoah

Niaz

et al. 2016

The Journal of Nutritional Biochemistry

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Colon cancer ranks third in cancer related mortalities in the United States. Many studies have investigated factors that contribute to colon cancer in which dietary and environmental factors have been shown to play an integral role in the etiology of this disease. Specifically, human dietary intake of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) has generated interest in looking at how it exerts its effects in gastrointestinal carcinogenesis. Therefore, the objective of this study was to investigate the preventative effects of olive oil on benzo(a)pyrene [B(a)P]-induced colon carcinogenesis in adult ApcMin mice. Mice were assigned to a control (n =8) or treatment group (n =8) consisting of 25, 50 and 100 μg B(a)P/kg body weight (bw) dissolved in tricaprylin [B(a)P-only group] or olive oil daily via oral gavage for sixty days. Our studies showed that ApcMin mice exposed to B(a)P developed a significantly higher number (p< 0.05) of larger dysplastic adenomas compared to those exposed to B(a)P + olive oil. Treatment of mice with B(a)P and olive oil significantly altered (p< 0.05) the expression of drug metabolizing enzymes in both the colon and liver tissues. However, only GST activity was significantly higher (p< 0.05) in the liver of mice treated with 50 and 100 μg B(a)P/kg bw + olive oil. Lastly, olive oil promoted rapid detoxification of B(a)P by decreasing its organic metabolite concentrations and also decreasing the extent of DNA damage to colon and liver tissues (p< 0.05). These results suggest that olive oil has a protective effect against B(a)P-induced colon tumors.

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“…Bars represent the average proportion of the genotypes for live, d12.5 embryos in vehicle-treated dams (n = 7, white bars) and PAH-treated dams (n = 9, black bars) and DMBA (unpublished observations, J. Detmar). Previous studies in rats have determined that after intravenous BaP exposure, this chemical demonstrated a long half-life in a number of different tissues [45] that can lead to persistence of DNA adducts in liver and lung tissue [46]. Therefore, it would appear that PAH exposure prior to pregnancy has long-lasting effects-at least with respect to spontaneous abortion and time to conception-likely due to accumulation of these compounds and their metabolites in various tissues.…”

Section: Discussionmentioning

confidence: 97%

Embryonic loss due to exposure to polycyclic aromatic hydrocarbons is mediated by Bax

et al. 2006

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The high miscarriage rates observed in women smokers raises the possibility that chemicals in cigarette smoke could be detrimental to embryo development. Previous studies have established that polycyclic aromatic hydrocarbons (PAHs), transactivate the arylhydrocarbon receptor (AhR), leading to cell death. Herein we show that PAH exposure results in murine embryo cell death, acting as a potential mechanism underlying cigarette-smoking-induced pregnancy loss. Cell death was preceded by increases in Bax levels, activation of caspase-3 and decreased litter size. Chronic exposure of females to PAHs prior to conception impaired development, resulting in a higher number of resorptions. This embryonic loss could not be prevented by the disruption of Hrk, but was diminished in embryos lacking Bax. We conclude that exposure of early embryos to PAHs reduces the allocation of cells to the embryonic and placental lineages by inducing apoptosis in a Bax-dependent manner, thus compromising the developmental potential of exposed embryos.

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Dose-dependent benzo(a)pyrene [B(a)P]–DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P

Cited by 30 publications

References 36 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

Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model

Embryonic loss due to exposure to polycyclic aromatic hydrocarbons is mediated by Bax

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