Dietary Accumulation Research Articles

Translocation of 14C-polystyrene nanoplastics into fish during a very-low concentration dietary exposure

Assessing the dietary accumulation of nanoplastics in animals following very-low exposure concentrations is restricted due to analytical limitations. This study adapted a method for synthesising semi-stable 14C-PS NPs (through styrene polymerisation) in small volumes for deployment in environmental studies. The method was developed with non-labelled material where the final polystyrene product had a primary particle size of 35 ± 8 nm (as measured by transmission electron microscopy). This method was then applied to 14C-labelled styrene to produce radiolabelled polystyrene nanoplastics (14C-PS NPs). The 14C-PS NPs were added (top-dressed) to a commercially available fish feed, with a measured concentration of 27.9 ± 2.1 kBq kg−1 (n = 5), equating to 5.9 μg polystyrene kg−1 feed. Fish (rainbow trout; Oncorhynchus mykiss) were fed this diet at a ration of 2% body weight per day for a period of two weeks. On day 3, 7 and 14, the fish were sampled for the mid intestine, hind intestine, kidney and liver, and measured for tissue radioactivity (determined by liquid scintillation counting). Some background activity was detected in the control samples (e.g., 1–16 and 4–11 Bq g−1 in the hind intestine and liver, respectively) which is due to natural background fluorescence. By the end of the experiment, the hind intestine and liver had significantly elevated radioactivity (25.3 and 15.0 Bq g−1, respectively) compared to the control, indicating the accumulation of nano polystyrene. In the liver, this equated to 1.8 μg polystyrene g−1 dry weight. This study confirms the accumulation of nano particles in vertebrates at low, environmentally relevant concentration, and highlights radiolabelling as a methodological approach suitable for exploring the bioaccumulation of nanoplastics and potential impacts.

The mercury flow through a terrestrial songbird food chain in subtropical pine forest: Elucidated by Bayesian isotope mixing model and stable mercury isotopes

In order to comprehend the transfer of inorganic mercury (IHg) and methylmercury (MeHg) within food chains in terrestrial pine forests, we collected samples of Great Tit nestlings, common invertebrates, plants, and soil in a subtropical pine forest and used Bayesian isotope mixing model analysis, Hg daily intake, and stable Hg isotopes to elucidate the flow of MeHg and IHg in these food chains. Results indicate that caterpillars and cockroaches are the predominant prey items for nestlings, accounting for a combined contribution of 81.5%. Furthermore, caterpillars, cockroaches, and spiders were found to contribute the most (∼80%) of both IHg and MeHg that dietary accumulated in nestlings. The provisoned invertebrates tend to supply more IHg and diluting the proportion of MeHg as total Hg (MeHg%). Notably, nestling feathers displayed the highest Δ199Hg values but a relatively lower MeHg%, suggesting an imbalanced incorporation of Hg from maternal transfer and dietary accumulation during the nestling stage. This study highlights the efficacy of nestlings as indicators for identifying Hg sources and transfers in avian species and food chains. However, caution must be exercised when using Hg isotope compositions in growing feathers, and the contribution of maternally transferred Hg should not be ignored.

Waterborne and dietary accumulation of well-dispersible hematite nanoparticles by zebrafish at different life stages

The widespread use of nanoparticles (NPs) has drawn considerable attention because of their potential toxicity and the environmental consequences thereof. However, the effects of the exposure route and life stage of an organism on the bioaccumulation and toxicity of NPs are largely unknown. In the present study, we investigated the accumulation kinetics (uptake, assimilation, and efflux) and tissue distribution of waterborne and dietary hematite NPs (HemNPs) during three life stages (embryo, larva, and adult) of the zebrafish Danio rerio. For all zebrafish life stages, the waterborne accumulation of well-dispersed HemNPs increased linearly with exposure time but decreased after reaching a maximum. The increase in HemNPs accumulation followed the order embryo > larva > adult. Compared with the waterborne route, the dietary accumulation of HemNPs in larval and adult zebrafish fluctuated, reaching a maximum after each food refreshment and then decreasing until the next food addition. Similar to waterborne exposure, adult fish accumulated less dietary HemNPs than did larvae. Nevertheless, dietary HemNPs mostly accumulated in the intestinal tract, with smaller amounts in the truncus, head, and gills, as compared with their waterborne counterparts. Moreover, in the gonad no dietary HemNPs were detected whereas accumulation via waterborne HemNPs was significant. Despite the low assimilation efficiency of dietary HemNPs, biodynamic modeling showed that the diet was the main source of particle accumulation in zebrafish. Thus, both the life stage and the exposure route should be considered in evaluations of the environmental risks of NPs.

Species-Specific (Hyalella azteca and Lymnea stagnalis) Dietary Accumulation of Gold Nano-particles Associated with Periphyton.

Ecological effects of gold nano-particles (AuNP) are examined due to growing use in consumer and industrial materials. This study investigated uptake and movement of AuNPs through an aquatic food chain. Simple (single-species) and diverse (multi-species) periphyton communities were exposed to AuNP (0, 100, 500µg L-1 treatments). AuNP quickly aggregated and precipitated from the water column, suggesting it is an insignificant route of AuNP exposure even at elevated concentrations. Gold was measured in 100 and 500µg L-1 periphyton treatments. Gold accumulation was similar between periphyton treatments, suggesting physical processes were important for AuNP basal accumulation. Hyalella azteca and Lymnea stagnalis whole body tissue analysis indicated gold accumulation may be attributed to different feeding mechanisms, general versus selective grazing, respectively. Results suggest trophic transfer of AuNP is organism specific and aggregation properties of AuNP are important when considering fate of nano-particles in the environment and movement through aquatic food webs.

Dietary Animal and Saturated Fat Predict Future Visceral Fat Accumulation in Japanese Americans

Both diet and visceral adiposity play key roles in cardiometabolic disease. However, the association between dietary fat and subsequent visceral fat accumulation is not known. Thus, we prospectively examined future visceral fat accumulation in relation to dietary intake of animal and plant fats, or saturated and polyunsaturated fats in 312 nondiabetic Japanese-American men and women. Visceral adiposity was measured as intra-abdominal fat (IAF) area at the umbilicus by computed tomography at baseline and 10-11 years. Detailed dietary information was assessed at baseline using a food frequency questionnaire and 24-hour recall. Insulin sensitivity was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR) and insulin response by the insulinogenic index (IGI) [Δinsulin/Δglucose (30-0 minutes)]. After adjustment for baseline IAF, age, sex, smoking habits (non-smokers, past-smokers, current smokers), physical activity, alcohol consumption, HOMA-IR, IGI, total protein intake, and total carbohydrate intake in multiple linear regression models, baseline log transformed animal fat intake [coefficient=15.319 (P=0.002)], but not plant fat intake [0.163 (P=0.270)], was associated with future IAF change. In the model that included saturated and polyunsaturated fat substituted for animal and plant fat intake, saturated fat was associated with future IAF change in both men [0.892 (P=0.030)] and women [1.121 (P=0.022)], but a statistically significant interaction was present between sex and polyunsaturated fat, such that polyunsaturated fat intake was inversely associated with future IAF change in men [-1.290 (P=0.003)], but not women [-0.058 (P=0.905)]. In conclusion, in both men and women, higher intake of animal fat and saturated fat, not plant fat, precede more visceral fat accumulation, while in men only, higher polyunsaturated fat intake precedes less visceral fat accumulation. Disclosure T. Hayashi: None. K. Sato: None. D.L. Leonetti: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim GmbH, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Research & Development, Merck & Co., Inc., Novo Nordisk A/S. S. Uehara: None. W.Y. Fujimoto: None. E.J. Boyko: None.

Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio)

The purpose of this study was to evaluate the effects of environmentally relevant dietary MeHg exposures on adult female yellow perch (Perca flavescens) and female zebrafish (Danio rerio) ovarian development and reproduction. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg following a whole life-cycle exposure. Chronic whole life dietary exposure of F1 zebrafish to MeHg mimics realistic wildlife exposure scenarios, and the twenty-week adult yellow perch exposure (where whole life-cycle exposures are difficult) captures early seasonal ovarian development. For both species, target dietary accumulation values were achieved prior to analyses. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-sequencing and quantitative real-time polymerase chain reaction (QPCR), but no significant phenotypic changes were observed regarding ovarian staging, fecundity, or embryo mortality. Yellow perch were exposed to dietary MeHg for 12, 16, or 20 weeks. In this species, a set of eight genes were assessed by QPCR in the pituitary, liver, and ovary, and no exposure-related changes were observed. The lack of genomic resources in yellow perch hinders the characterization of subtle molecular impacts. The ovarian somatic index, circulating estradiol and testosterone, and ovarian staging were not significantly altered by MeHg exposure in yellow perch. These results suggest that environmentally relevant MeHg exposures do not drastically reduce the reproductively important endpoints in these fish, but to capture realistic exposure scenarios, whole life-cycle yellow perch exposures are needed.

Waterborne and Dietary Copper Accumulation in Various Tissues of Oreochromis niloticus

Waterborne and Dietary Copper Accumulation in Various Tissues of Oreochromis niloticus

Dietary Accumulation of Inorganic Selenium by a Larval Amphibian (Hyla chrysoscelis) and Influence on Accumulation of Background Mercury.

Larval gray tree frogs (Hyla chrysoscelis) were exposed to inorganic Se (SeO2) added to the diet (10.2 and 86.3ug/g dw) and monitored for accumulation and effect. Background concentrations of Hg were also measured in food and carcasses to assess possible effects of Se on Hg accumulation. Selenium was accumulated in a dose dependent manner, and life stages did not differ. No effects of Se exposure were observed on survival, growth, or time to metamorphosis. Mercury concentrations in carcasses, resulting from background concentrations in food, were significantly affected by the presence of Se. In the high Se treatment, Hg concentrations were significantly decreased relative to those in the low Se treatment and the control. Our study suggests that exposure to inorganic Se as SeO2 at the concentrations tested do not elicit adverse biological effects, but exposure to relatively high concentrations of Se may reduce accumulation of Hg from food.

Using energy budgets to combine ecology and toxicology in a mammalian sentinel species

Process-driven modelling approaches can resolve many of the shortcomings of traditional descriptive and non-mechanistic toxicology. We developed a simple dynamic energy budget (DEB) model for the mink (Mustela vison), a sentinel species in mammalian toxicology, which coupled animal physiology, ecology and toxicology, in order to mechanistically investigate the accumulation and adverse effects of lifelong dietary exposure to persistent environmental toxicants, most notably polychlorinated biphenyls (PCBs). Our novel mammalian DEB model accurately predicted, based on energy allocations to the interconnected metabolic processes of growth, development, maintenance and reproduction, lifelong patterns in mink growth, reproductive performance and dietary accumulation of PCBs as reported in the literature. Our model results were consistent with empirical data from captive and free-ranging studies in mink and other wildlife and suggest that PCB exposure can have significant population-level impacts resulting from targeted effects on fetal toxicity, kit mortality and growth and development. Our approach provides a simple and cross-species framework to explore the mechanistic interactions of physiological processes and ecotoxicology, thus allowing for a deeper understanding and interpretation of stressor-induced adverse effects at all levels of biological organization.

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals.

Dietary accumulation of tetrabromobisphenol A and its effects on the scallop Chlamys farreri

Tetrabromobisphenol A (TBBPA) is currently the most widely-used brominated flame retardant (BFR) and has been proven to have a very high toxicity to aquatic organisms including bivalves. In this study, a laboratory experiment was conducted to obtain a better understanding of the role of algae food on the bioaccumulation of TBBPA and its effects on the suspension-feeding bivalve, the scallop, Chlamys farreri. Scallops were exposed to TBBPA via algae food alone or food+water for 10days. Results showed that TBBPA was accumulated rapidly by scallops, reaching an approximate steady state in soft tissues within 3days. The primary route of TBBPA accumulation was via the water, while dietary uptake was relatively minor. TBBPA exposure led to significant inhibition on microsomal cytochrome P450 and cytochrome b5 levels in gills and digestive gland, whereas GST activity and GSH level increased significantly, which indicated that TBBPA could be a suitable substrate to directly participate in phase II metabolism. TBBPA clearly induced the activity of SOD, suggesting the oxidant stress induced by TBBPA. This study suggests that dietary uptake was not the predominant uptake route for TBBPA in bivalves and also provides a preliminary basis for studying the detoxification and antioxidant responses of marine bivalves upon exposure to TBBPA.

Progress toward understanding the bioaccumulation of perfluorinated alkyl acids

Progress toward understanding the bioaccumulation of perfluorinated alkyl acids

Dietary bioavailability of cadmium presented to the gastropod Peringia ulvae as quantum dots and in ionic form

For quantum dots (QDs) synthesized in solvents that are immiscible in water, dietary, rather than aqueous, exposure is expected to be the primary route of uptake. The estuarine snail Peringia ulvae was presented with mats of simulated detritus spiked with oleic acid capped cadmium sulfide (CdS; 3.1 ± 0.4 nm) or cadmium selenide (CdSe; 4.2 ± 0.8 nm) nanoparticles, synthesized using a microfluidics method, or Cd(2+) (added as Cd[NO3 ]2 ) as a control. A biodynamic modeling approach was used to quantify parameters that describe the dietary accumulation of the Cd forms. Ingestion rates decreased across treatments at higher exposure concentrations, indicating a metal-induced stress response related to Cd dose rather than form. Although Cd was bioavailable from both CdS and CdSe QDs, uptake rate constants from diet were significantly lower than that of Cd(2+) (p < 0.05). After 72 h depuration, however, no loss of Cd was observed from snails that had accumulated Cd from either type of QD. In comparison, snails ingesting Cd(2+) -spiked detritus eliminated 39% of their accumulated body burden per day. The almost identical uptake and efflux rates for Cd in both QDs suggest no effect of the chalcogenide conjugates (S or Se). The findings of the present study indicate that the availability of Cd in the form of nanoparticles and its apparent in vivo persistence will lead to bioaccumulation. The implications of this are discussed.

Evidence of Maternal Offloading of Organic Contaminants in White Sharks (Carcharodon carcharias)

Organic contaminants were measured in young of the year (YOY) white sharks (Carcharodon carcharias) incidentally caught in southern California between 2005 and 2012 (n = 20) and were found to be unexpectedly high considering the young age and dietary preferences of young white sharks, suggesting these levels may be due to exposure in utero. To assess the potential contributions of dietary exposure to the observed levels, a five-parameter bioaccumulation model was used to estimate the total loads a newborn shark would potentially accumulate in one year from consuming contaminated prey from southern California. Maximum simulated dietary accumulation of DDTs and PCBs were 25.1 and 4.73 µg/g wet weight (ww) liver, respectively. Observed ΣDDT and ΣPCB concentrations (95±91 µg/g and 16±10 µg/g ww, respectively) in a majority of YOY sharks were substantially higher than the model predictions suggesting an additional source of contaminant exposure beyond foraging. Maternal offloading of organic contaminants during reproduction has been noted in other apex predators, but this is the first evidence of transfer in a matrotrophic shark. While there are signs of white shark population recovery in the eastern Pacific, the long-term physiological and population level consequences of biomagnification and maternal offloading of environmental contaminants in white sharks is unclear.

Accumulation of polychlorinated biphenyls from contaminated sediment by Atlantic cod (Gadus morhua): Direct accumulation from resuspended sediment and dietary accumulation via the polychaeteNereis virens

Bioaccumulation of sediment-associated polychlorinated biphenyls (PCBs) was examined in Atlantic cod (Gadus morhua) through direct diffusion from the sediment (via the water phase) and through the food chain (dietary exposure). To facilitate direct accumulation from the sediment, it was continuously resuspended. To study the dietary bioaccumulation of PCBs, cod were fed benthic polychaetes (Nereis virens) previously exposed to test sediments, which were naturally polluted sediments from the inner Oslofjord (Norway). Both exposure experiments had a duration of 129 d. Furthermore, the role of sediments as a source of PCBs accumulated in Oslofjord cod was elucidated, using results from environmental monitoring as a reference. Generally, the results suggest that the contaminated sediments of the inner Oslofjord are an important source of legacy PCBs for accumulation in resident cod, although additional contributions may also be important. Crude estimates of assimilation efficiency of ingested PCBs (through diet) were found to be 30 to 50%; the highest was for the lower chlorinated congeners (PCB-28 and -52). Challenges for applying trophic magnification factors for determining biomagnification in laboratory experiments, in terms of preventive environmental safety, are indicated. The results provide useful information for parameterization of models describing the behavior of hydrophobic persistent contaminants in the foodweb of the Oslofjord and elsewhere.

Dietary (periphyton) and aqueous Zn bioaccumulation dynamics in the mayfly Centroptilum triangulifer

Diet is often the predominant route of trace metal exposure in aquatic insects. In freshwater ecosystems, periphyton serves as a primary source of food to many aquatic insects and is a major sink for trace metals. We investigated the bioconcentration of the essential metal Zn by periphyton using (65)Zn as a radiotracer. At relatively low dissolved concentrations (2-20 μg L(-1)), non steady state Zn bioconcentration by periphyton averaged 6,099 ± 2,430-fold, with much of the variability determined by loading regime (number of renewals and duration of exposures). Labeled periphyton was used as a food source for dietary accumulation studies with the mayfly Centroptilum triangulifer. After 29 days, larvae concentrated Zn 19-, 16- and 17-fold relative to dietary Zn concentrations of 8.1, 43.2 and 82.3 μg g(-1) (dry weight), respectively. Adults from that same cohort only concentrated Zn 8-, 3- and 3- fold relative to those same dietary concentrations, revealing that mayflies lose significant Zn prior to reaching adulthood. Anecdotal evidence suggests that this loss occurs prior to emergence to the subimago, as negligible Zn was found in the subimago to imago exuvium. Across a range of adult tissue concentrations, maternal transfer consistently averaged 26.7 %. Uptake (k(u), 0.26 L g(-1 )d(-1)) and efflux rate constants (k(e), 0.001-0.007 d(-1)) were measured and assimilation efficiencies from dietary Zn concentrations of 4.9 and 59.7 μg Zn g(-1) were estimated to be 88 ± 4 % and 64 ± 15 %, respectively. Both life cycle and biodynamic modeling approaches point towards diet being the primary route of Zn bioaccumulation in this mayfly.

Immunomodulation in eastern oysters, Crassostrea virginica, exposed to a PAH-contaminated, microphytobenthic diatom

The trophic transfer of sediment-associated pollutants is a growing concern in shellfish harvesting areas. Previous studies have examined the role of phytoplankton in the transport of organic contaminants to bivalve species, but little information on microphytobenthic communities and their role as contaminant vectors exists. Polycyclic aromatic hydrocarbons (PAHs) are organic compounds formed during natural and industrial processes; they are termed “persistent organic pollutants” because they are only slowly degraded by natural processes. This study examined the transfer of PAH compounds (naphthalene, pyrene, and benzo(a)pyrene) by a microphytobenthic diatom to the eastern oyster, a commercially important shellfish species, to determine if dietary accumulation is a route of contaminant exposure capable of inducing physiological responses. PAH compounds were adsorbed to a diatom culture (Nitzschia brevirostris) in a range of concentrations (5, 125, 625, and 1000μgL−1), and eastern oysters were exposed experimentally to the contaminated diatom cultures to assess possible effects upon oyster hemocytes and selected immune-defense functions. A preliminary experiment was designed to identify individual effects of several PAH compounds (naphthalene, pyrene, and benzo(a)pyrene) on hemocyte viability and phagocytic activity. Results from this experiment revealed that the most-toxic compound, benzo(a)pyrene, at the highest concentration, stimulated an increase in agranular hemocyte counts. A follow-up study examined the effects of benzo(a)pyrene on hemocyte viability, adhesion, phagocytosis, and reactive oxygen species (ROS). These studies showed the ability of this benthic diatom to transport PAHs to the eastern oyster and to cause immunomodulation. Hemocyte responses to dietary PAH exposure included an increase in circulating hemocytes and increased production of reactive oxygen species by these cells.

Contrasting mercury accumulation patterns in tilapia (Oreochromis niloticus) and implications on somatic growth dilution

Dietary ingestion constitutes a major pathway for mercury (Hg) accumulation in freshwater fish, thus the ingestion rate (IR) may greatly influence the Hg bioaccumulation through its effect on Hg influx and other biokinetic processes. To explore the complex influence of IR, we conducted long-term bioaccumulation experiments by accurately controlling the IRs in the freshwater tilapia (Oreochromis niloticus). The dietary accumulation of both inorganic mercury (Hg[II]) and methylmercury (MeHg) in tilapia under different IRs was monitored over a period of 30 days by feeding the fish with uniformly radiolabeled crustaceans. The biokinetic parameters under various IRs were concurrently determined. With the increase of IR from 0.01gg−1d−1 to 0.12gg−1d−1, the dietary assimilation efficiency of Hg(II) in the tilapia decreased by 43% while the elimination rate increased by a factor of 1.8; both biokinetic changes slowed down the overall Hg(II) bioaccumulation at high IRs. In contrast to Hg(II), the biokinetics of MeHg was not significantly influenced, but its bioaccumulation increased disproportionally with increasing IR, showing slower increase at higher IR. We then employed a biokinetic model to simulate the long-term mercury bioaccumulation patterns in tilapia at various IRs. The modeling results indicated that the growth effect could not be ignored in long-term accumulation process. A rapid growth of fish driven by food availability could significantly reduce the MeHg concentrations in the tilapia. Our results demonstrated for the first time the contrasting influences of dietary ingestion on the long-term bioaccumulation of Hg(II) and MeHg. The somatic growth dilution was much more likely to occur for MeHg than for Hg(II).

P4-02-01: Bis(2-Ethylhexyl) Phthalate: A Potential Endocrine Disruptor Confer Letrozole Insensitivity and Induction of Aromatase Activity in Breast Cancer Cells.

Abstract Exposure to endocrine disrupting compounds (EDC's) is an important determinant of mammary gland development and mammary tumor pathogenesis. The risk of breast cancer in adulthood is known to be influenced by environmental factors experienced as a fetus. Fetal exposure to dietary factors or certain pharmaceuticals and environmental chemicals that affect or mimic steroid hormones increase predisposition to breast cancer. The mechanisms by which EDC's alter epigenetic programming, differentiation and deregulation of ductal branching of mammary glands are poorly understood. A high ratio of estrogen receptor a (ERα) to ERβ has been recently found to be associated with poor prognosis and aggressive disease in breast cancer patients. Preliminary studies from our laboratory revealed that bis(2-ethylhexyl) phthalate (DEHP) is a possible EDC which induces cell proliferation in T47D, MCF7, MCF7/Aro breast cancer cells in vitro and confers insensitivity to letrozole, a third generation aromatase inhibitor. DEHP increased cell proliferation (MTT assay) in a dose dependent manner and was non toxic to T47D, MCF7 and MCF 7 Aro cells. 1, 10 and 100 nM concentrations of DEHP up regulated ERα and down regulated ERβ at the mRNA level. Hypermethylation in the estrogen receptor beta (ERβ) promoter was observed after treatment with 1nM DEHP for 24 h, suggesting that DEHP alter epigenetic programming through changes in the DNA methylation to modify the chromatin structure and change the accessibility of DNA to transcription factors. When breast cancer cells were treated with letrozole (200nM and DEHP (1nM) together, they survived, whereas those treated with letrozole alone did not survive. Aromatase mRNA and enzyme levels were higher in the DEHP treated cells by comparison with sham control MCF7/Aro cells. Nonmalignant MCF-10A breast epithelial cells showed a proliferation advantage (MTT assay) by up regulation of ERα as well as aromatase expression when treated with 1nM DEHP. Aromatase transgenic mice treated with 10mg/Kg b.wt of DEHP over a period of 30 days resulted in the excessive ductal branching density and epithelial outgrowth in the mammary gland. The present data suggest that dietary accumulation of DEHP through plastic food containers, water bottles, etc. may contribute to risk of hormone sensitive breast cancer in women and chemoinsensitivity and or drug resistance in breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-01.

Bioaccumulation and trophic transfer of dioxins in marine copepods and fish

Despite the great concerns about dioxins in the marine environments, the biokinetics and bioaccumulation of these compounds in marine organisms remains little known. Using radioactive tracers the aqueous uptake, dietary assimilation efficiency, and elimination of dioxins were measured in marine phytoplankton, copepods and seabream. The calculated uptake rate constant of dioxins decreased with increasing trophic levels, whereas the dietary assimilation efficiency (AE) was 28.5–57.6% in the copepods and 36.6–70.2% in the fish. The dietary AE was highly dependent on the food concentrations and food type. The elimination rate constant of dioxin in the copepods varied with different exposure pathways as well as food concentration and food type. Biokinetic calculation showed that dietary accumulation was the predominant pathway for dioxin accumulation in marine copepods and fish. Aqueous uptake can be an important pathway only when the bioconcentration of dioxins in the phytoplankton was low.