Differences In Metabolic Capacity Research Articles

A comparative and ontogenetic examination of mitochondrial function in Antarctic notothenioid species

Notothenioidei fishes have evolved under stable cold temperatures; however, ocean conditions are changing globally, with polar regions poised to experience the greatest changes in environmental factors, such as warming. These stressors have the potential to dramatically affect energetic demands, and the persistence of the notothenioids will be dependent on metabolic capacity, or the ability to match energy supply with energy demand, to restore homeostasis in the face of changing climate conditions. In this study we examined aerobic metabolic capacity in three species, Trematomus bernacchii, T. pennellii and T. newnesi, and between two life stages, juvenile and adult, by assessing mitochondrial function of permeabilized cardiac fibers. Respiratory capacity differed among the adult notothenioids in this study, with greater oxidative phosphorylation (OXPHOS) respiration in the pelagic T. newnesi than the benthic T. bernacchii and T. pennellii. The variation in mitochondrial respiratory capacity was likely driven by differences in the mitochondrial content, as measured by citrate synthase activity, which was the highest in T. newnesi. In addition to high OXPHOS, T. newnesi exhibited lower LEAK respiration, resulting in greater mitochondrial efficiency than either T. bernacchii or T. pennellii. Life stage largely had an effect on mitochondrial efficiency and excess complex IV capacity, but there were little differences in OXPHOS respiration and electron transfer capacity, pointing to a lack of significant differences in the metabolic capacity between juveniles and adults. Overall, these results demonstrate species-specific differences in cardiac metabolic capacity, which may influence the acclimation potential of notothenioid fishes to changing environmental conditions.

Graph-based and constraint-based heterologous metabolic pathway design methods and application

It is among the goals in metabolic engineering to construct microbial cell factories producing high-yield and high value-added target products, and an important solution is to design efficient synthetic pathway for the target products. However, due to the difference in metabolic capacity among microbial chassises, the available substrate and the yielded products are limited. Therefore, it is urgent to design related metabolic pathways to improve the production capacity. Existing metabolic engineering approaches to designing heterologous pathways are mainly based on biological experience, which are inefficient. Moreover, the yielded results are in no way comprehensive. However, systems biology provides new methods for heterologous pathway design, particularly the graph-based and constraint-based methods. Based on the databases containing rich metabolism information, they search for and uncover possible metabolic pathways with designated strategy (graph-based method) or algorithm (constraint-based method) and then screen out the optimal pathway to guide the modification of strains. In this paper, we reviewed the databases and algorithms for pathway design, and the applications in metabolic engineering and discussed the strengths and weaknesses of existing algorithms in practical application, hoping to provide a reference for the selection of optimal methods for the design of product synthesis pathway.

Histogram analysis of 18F-FDG PET imaging SUVs may predict the histologic grade of oral squamous cell carcinoma

We tested the hypothesis that histogram analysis parameters of standardized uptake values (SUVs) obtained preoperatively using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) are significantly influenced by differences in metabolic capacity due to the histologic grade of oral squamous cell carcinoma (OSCC). The study included 62 patients who were clinically diagnosed with OSCC and received surgical treatment after an 18F-FDG PET examination. Histogram analysis was performed using all voxels contained in the tumor area of each patient with an SUV ≥2.5. The histogram parameters calculated were the mean and standard deviation of SUVs, maximum SUV, metabolic tumor volume, skewness, and kurtosis. Statistical analyses were performed using a Mann-Whitney U test to calculate the significance of differences in these parameters between groups with well- and moderately- or poorly-differentiated tumors. Statistical significance was assumed at P < .05. Only a comparison of kurtosis in the histogram showed a significant difference between the well- and moderately/poorly-differentiated tumors (P=.0294). The distribution of metabolic capacity in oral squamous cell carcinoma tissues revealed on an 18F-FDG PET examination may help identify the histologic grade. This finding may provide valuable information for determining the subsequent treatment plan and predicting disease prognosis.

An in vitro model for microbial fructoselysine degradation shows substantial interindividual differences in metabolic capacities of human fecal slurries

Fructoselysine is formed upon heating during processing of food products, and being a key intermediate in advanced glycation end product formation considered to be potentially hazardous to human health. Human gut microbes can degrade fructoselysine to yield the short chain fatty acid butyrate. However, quantitative information on these biochemical reactions is lacking, and interindividual differences therein are not well established. Anaerobic incubations with pooled and individual human fecal slurries were optimized and applied to derive quantitative kinetic information for these biochemical reactions. Of 16 individuals tested, 11 were fructoselysine metabolizers, with Vmax, Km and kcat-values varying up to 14.6-fold, 9.5-fold, and 4.4-fold, respectively. Following fructoselysine exposure, 10 of these 11 metabolizers produced significantly increased butyrate concentrations, varying up to 8.6-fold. Bacterial taxonomic profiling of the fecal samples revealed differential abundant taxa for these reactions (e.g. families Ruminococcaceae, Christenellaceae), and Ruminococcus_1 showed the strongest correlation with fructoselysine degradation and butyrate production (ρ ≥ 0.8).This study highlights substantial interindividual differences in gut microbial degradation of fructoselysine. The presented method allows for quantification of gut microbial degradation kinetics for foodborne xenobiotics, and interindividual differences therein, which can be used to refine prediction of internal exposure.

Physiologically Based Pharmacokinetic Modeling in Risk Assessment: Case Study With Pyrethroids.

The assessment of potentially sensitive populations is an important application of risk assessment. To address the concern for age-related sensitivity to pyrethroid insecticides, life-stage physiologically based pharmacokinetic (PBPK) modeling supported by in vitro to in vivo extrapolation was conducted to predict age-dependent changes in target tissue exposure to 8 pyrethroids. The purpose of this age-dependent dosimetry was to calculate a Data-derived Extrapolation Factor (DDEF) to address age-related pharmacokinetic differences for pyrethroids in humans. We developed a generic human PBPK model for pyrethroids based on our previously published rat model that was developed with in vivo rat data. The results demonstrated that the age-related differences in internal exposure to pyrethroids in the brain are largely determined by the differences in metabolic capacity and in physiology for pyrethroids between children and adults. The most important conclusion from our research is that, given an identical external exposure, the internal (target tissue) concentration is equal or lower in children than in adults in response to the same level of exposure to a pyrethroid. Our results show that, based on the use of the life-stage PBPK models with 8 pyrethroids, DDEF values are essentially close to 1, resulting in a DDEF for age-related pharmacokinetic differences of 1. For risk assessment purposes, this indicates that no additional adjustment factor is necessary to account for age-related pharmacokinetic differences for these pyrethroids.

Interspecies comparison of the residue levels and profiles of persistent organic pollutants in terrestrial top predators

Serum samples from three species of living terrestrial top predators were analysed for six groups of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and polybrominated diphenyl ethers (PBDEs). The study included three carnivore species: lion (Panthera leo), hyena (Hyena brunnea) and cheetah (Acinonyx jubatus). All samples were collected from healthy living animals between 2004 and 2005. Most of the samples (wild lions (n = 50) and hyenas (n = 11)) were collected from various locations within the Kruger National Park and Addo National Park (South Africa), while captive lions (n = 6) and cheetahs (n = 3) were collected from the Antwerp Zoo (Belgium). In general, relatively low levels of POPs were found in the studied species, varying widely within species and locations. Median concentrations of POPs were higher in captive lions (PCBs: 505 pg/mL; DDTs: 270 pg/mL; HCHs: 72 pg/mL; HCB: 34 pg/mL; CHLs: 24 pg/mL; PBDEs: 8 pg/mL) compared to wild lions (DDTs: 274 pg/mL; HCHs: 44 pg/mL; CHLs: 7.9 pg/mL; PCBs: 2.1 pg/mL; HCB: < LOQ; PBDEs: < LOQ). In the wild animals, POPs accumulated in the following order: DDTs > HCHs > CHLs > HCB > PCBs > PBDEs, while in the captive animals, the order was: PCBs > DDTs > CHLs > HCHs > HCB > PBDEs, suggesting differences in the diet of these animals. Furthermore, wild hyena contained significantly higher (p < 0.05) median levels of POPs compared to wild lions, possibly reflecting differences in metabolic capacity and/or feeding habits, together with an uneven distribution of POPs in the area where the animals lived. No previous data are available to compare for similar terrestrial top predators, such as lion, hyena and cheetah. To our knowledge, this is first study on POPs in these three species. The low POP levels found in this study were several orders of magnitude lower than those for other carnivore species, such as polar bears, grizzly bears, brown bears and wolves worldwide. The present study has revealed the need for expanding research and monitoring on occurrence, levels and disposition of POPs in the top predators of the terrestrial environment.

Sex-specific effects of blood cadmium on thyroid hormones and thyroid function status: Korean nationwide cross-sectional study

Previous studies on blood cadmium (BCd) and changes in thyroid hormone levels are controversial. We investigated whether thyroid hormone levels and thyroid function status were associated with BCd according to sex in the Korean population. Our study included 1972 participants based on the 2013 Korea National Health and Nutrition Examination Survey (KNHANES) data. Participants whose thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels were altered physiologically or medically were excluded. Changes in TSH, fT4, and anti-thyroid peroxidase antibody (TPOAb) in men and women were analyzed by different characteristics: age, body mass index (BMI), smoking status, drinking status, BCd, and urine iodine-to-creatinine ratio (UI/Cre). Thyroid function status was classified as hypothyroidism, euthyroidism, and hyperthyroidism as defined by TSH and fT4 levels. Among the total participants, there was a negative correlation between BCd and fT4 (r=-0.067, p = 0.003). In men (n = 1057), fT4 levels decreased with increasing BCd quartile (p-for-trend = 0.002). After adjustment for age, BMI, smoking status, UI/Cre, and TPOAb, the association between BCd and hypothyroidism was significant in men (odds ratio = 1.813, p = 0.032) but not in women. These results suggest that cadmium accumulation is closely associated with thyroid dysfunction, and there is a difference in metabolic capacity according to sex.

Metabolism of N-Methyl-2-Pyrrolidone in Honey Bee Adults and Larvae: Exploring Age Related Differences in Toxic Effects

In chronic feeding assays, the common agrochemical inert formulant N-methyl-2-pyrrolidone (NMP) is at least 20 times more toxic to honey bee larvae than to adults, but the underlying cause of this difference is unknown. In other taxa, NMP is primarily detoxified via a cytochrome P450 mediated pathway. Using a LC-MS method, putative cytochrome P450 metabolites of NMP were identified and quantified in adults and larvae following chronic exposure to NMP. Major differences in the identities and quantities of the generated metabolites were observed between adults and larvae. One major difference was the higher percentage of the administered NMP recovered as the parent compound in larvae compared to adults. To further explore the apparent difference in metabolic capacity, a spectrofluorometric method was used to compare general cytochrome P450 enzyme activity by monitoring the transformation of a 7-ethoxycoumarin substrate. Higher microsomal levels of 7-ethoxycoumarin-O-deethylase activity in adult fat bodies suggests that the higher percentage of unmetabolized NMP in larvae relative to adults may be due to lower cytochrome P450 enzyme activity in fat bodies. Taken together, these results suggest that larvae may be less able to detoxify xenobiotics encountered in diet than adults, and these findings will help inform future risk assessment.

Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in Cmax, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in Cmax and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

On the reversibility of parasitism: adaptation to a free-living lifestyle via gene acquisitions in the diplomonad Trepomonas sp. PC1.

BackgroundIt is generally thought that the evolutionary transition to parasitism is irreversible because it is associated with the loss of functions needed for a free-living lifestyle. Nevertheless, free-living taxa are sometimes nested within parasite clades in phylogenetic trees, which could indicate that they are secondarily free-living. Herein, we test this hypothesis by studying the genomic basis for evolutionary transitions between lifestyles in diplomonads, a group of anaerobic eukaryotes. Most described diplomonads are intestinal parasites or commensals of various animals, but there are also free-living diplomonads found in oxygen-poor environments such as marine and freshwater sediments. All these nest well within groups of parasitic diplomonads in phylogenetic trees, suggesting that they could be secondarily free-living.ResultsWe present a transcriptome study of Trepomonas sp. PC1, a diplomonad isolated from marine sediment. Analysis of the metabolic genes revealed a number of proteins involved in degradation of the bacterial membrane and cell wall, as well as an extended set of enzymes involved in carbohydrate degradation and nucleotide metabolism. Phylogenetic analyses showed that most of the differences in metabolic capacity between free-living Trepomonas and the parasitic diplomonads are due to recent acquisitions of bacterial genes via gene transfer. Interestingly, one of the acquired genes encodes a ribonucleotide reductase, which frees Trepomonas from the need to scavenge deoxyribonucleosides. The transcriptome included a gene encoding squalene-tetrahymanol cyclase. This enzyme synthesizes the sterol substitute tetrahymanol in the absence of oxygen, potentially allowing Trepomonas to thrive under anaerobic conditions as a free-living bacterivore, without depending on sterols from other eukaryotes.ConclusionsOur findings are consistent with the phylogenetic evidence that the last common ancestor of diplomonads was dependent on a host and that Trepomonas has adapted secondarily to a free-living lifestyle. We believe that similar studies of other groups where free-living taxa are nested within parasites could reveal more examples of secondarily free-living eukaryotes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0284-z) contains supplementary material, which is available to authorized users.

Metatranscriptome analyses indicate resource partitioning between diatoms in the field

Diverse communities of marine phytoplankton carry out half of global primary production. The vast diversity of the phytoplankton has long perplexed ecologists because these organisms coexist in an isotropic environment while competing for the same basic resources (e.g., inorganic nutrients). Differential niche partitioning of resources is one hypothesis to explain this "paradox of the plankton," but it is difficult to quantify and track variation in phytoplankton metabolism in situ. Here, we use quantitative metatranscriptome analyses to examine pathways of nitrogen (N) and phosphorus (P) metabolism in diatoms that cooccur regularly in an estuary on the east coast of the United States (Narragansett Bay). Expression of known N and P metabolic pathways varied between diatoms, indicating apparent differences in resource utilization capacity that may prevent direct competition. Nutrient amendment incubations skewed N/P ratios, elucidating nutrient-responsive patterns of expression and facilitating a quantitative comparison between diatoms. The resource-responsive (RR) gene sets deviated in composition from the metabolic profile of the organism, being enriched in genes associated with N and P metabolism. Expression of the RR gene set varied over time and differed significantly between diatoms, resulting in opposite transcriptional responses to the same environment. Apparent differences in metabolic capacity and the expression of that capacity in the environment suggest that diatom-specific resource partitioning was occurring in Narragansett Bay. This high-resolution approach highlights the molecular underpinnings of diatom resource utilization and how cooccurring diatoms adjust their cellular physiology to partition their niche space.

Interspecies Comparison of Chlorinated Contaminant Concentrations and Profiles in Wild Terrestrial Mammals from Northwest Poland

The aim of this study was to determine residual polychlorinated biphenyls (PCBs) and organochlorine pesticides in the adipose tissue of wild terrestrial mammals coming from the same area in northwest Poland and to compare the organochlorine content and profile between species. The study was performed on five mammalian species, including omnivores (badger, wild boar, raccoon dog) and herbivores (roe deer, red deer). The obtained results show that the levels of residues of most of the analyzed compounds were greater in omnivorous mammals than herbivorous mammals. We found differences in the pattern of accumulation of organochlorines. In the raccoon dog organochlorines accumulated in the following descending order: DDTs > PCBs > HCHs > endrin > dieldrin; in the badger, wild boar, and roe deer, the order was as follows: DDTs > HCHs > PCBs > endrin > dieldrin; and in red deer, the order was as follows: HCHs > DDTs > PCBs > endrin > dieldrin. PCB 153 was dominant in herbivores and in the wild boar, whereas in the raccoon dog it was lower than PCB 138 and in badger lower than PCB 180. These differences in the tested species may reflect differences in metabolic capacity and/or feeding habits and an uneven distribution of organochlorines in the area where the animals lived. Maximum residue levels (MRLs) were exceeded in single samples from animals whose meat and fat can be consumed by humans. The greatest number of cases where MRLs were exceeded was observed in the adipose tissue of the badger (HCHs, DDTs, endrin, non-dioxin-like PCBs) and the fewest in the adipose tissue of roe deer (only lindane).

Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers

This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Microsomal lipase activity was significantly lower in humans than in mice. The V max/K m value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.

Application of an Updated Physiologically Based Pharmacokinetic Model for Chloroform to Evaluate CYP2E1-Mediated Renal Toxicity in Rats and Mice

Physiologically based pharmacokinetic (PBPK) models are tools for interpreting toxicological data and extrapolating observations across species and route of exposure. Chloroform (CHCl(3)) is a chemical for which there are PBPK models available in different species and multiple sites of toxicity. Because chloroform induces toxic effects in the liver and kidneys via production of reactive metabolites, proper characterization of metabolism in these tissues is essential for risk assessment. Although hepatic metabolism of chloroform is adequately described by these models, there is higher uncertainty for renal metabolism due to a lack of species-specific data and direct measurements of renal metabolism. Furthermore, models typically fail to account for regional differences in metabolic capacity within the kidney. Mischaracterization of renal metabolism may have a negligible effect on systemic chloroform levels, but it is anticipated to have a significant impact on the estimated site-specific production of reactive metabolites. In this article, rate parameters for chloroform metabolism in the kidney are revised for rats, mice, and humans. New in vitro data were collected in mice and humans for this purpose and are presented here. The revised PBPK model is used to interpret data of chloroform-induced kidney toxicity in rats and mice exposed via inhalation and drinking water. Benchmark dose (BMD) modeling is used to characterize the dose-response relationship of kidney toxicity markers as a function of PBPK-derived internal kidney dose. Applying the PBPK model, it was also possible to characterize the dose response for a recent data set of rats exposed via multiple routes simultaneously. Consistent BMD modeling results were observed regardless of species or route of exposure.

Selective breeding of mice for high voluntary exercise alters adaptive plasticity of metabolic phenotypes in skeletal muscle

The response to selection on behavior necessarily entails associated changes in lower‐level (subordinate) traits. We studied mice from 4 replicate lines that had been selectively bred for high levels of voluntary exercise (High Runner or HR) that run ~3‐fold more wheel revolutions/day than those from 4 non‐selected control (C) lines, and have evolved higher baseline endurance and VO2max. We examined hindlimb skeletal muscle metabolic capacity in mice housed with or without wheel access for 8 weeks. Triceps surae muscles were assayed at 37C for Vmax of hexokinase (HK), citrate synthase (CS), carnitine palmitoyl‐transferase (CPT), and β‐hydroxyacyl‐CoA dehydrogenase (HAD). Wheel access increased heart ventricle mass in both HR and C lines, but only HR showed increased enzyme activities as well as higher phosphorylation of 5ˈ‐AMP‐activated protein kinase. Analysis of wheel‐access groups indicated the greater training effect in HR could be explained statistically by their greater wheel running for ventricle mass, CS, and HAD, but for HK and CPT, HR mice had greater adaptive plasticity of the response to voluntary exercise. Thus, HR do not have inherent baseline differences in metabolic capacity, but they have evolved greater adaptive plasticity for some traits. Supported by NSF IOB‐0543429 and IOS‐1121273 to TG.

Variation in expression of calcium-handling proteins is associated with inter-individual differences in mechanical performance of rat (Rattus norvegicus) skeletal muscle

An important constraint on locomotor performance is the trade-off between sprint and endurance performance. One intuitive explanation for this trade-off is that an individual muscle cannot excel at generating both maximal force/power and high fatigue resistance. The underlying reasons for this muscle trade-off are poorly defined. The aim of this study was to test the hypothesis that inter-individual variation in muscle mechanics is associated with inter-individual differences in metabolic capacities and expression of calcium-handling proteins. Lateral gastrocnemius muscles were isolated from 20 rats (Rattus norvegicus) and analysed to determine metabolic capacity, sarco/endoplasmic reticulum calcium ATPase (SERCA)1 protein concentration, total SERCA activity, and mRNA concentrations of SERCA1, SERCA2, troponin I and ryanodine receptors. Isometric studies of lateral gastrocnemius muscles at 30°C showed that muscles with higher sprint performance had lower fatigue resistance. More rapid muscle contraction was correlated with higher lactate dehydrogenase activity and increased expression of ryanodine receptor 1. More rapid muscle relaxation was correlated with increased expression of troponin I type 2 (fast) isoform and decreased expression of SERCA2 (slow) isoform. Treating muscles with dantrolene confirmed that ryanodine receptor activity is important in determining tetanus force and muscle contraction rates, but has no effect on fatigue resistance. Thapsigargin treatment revealed that SERCA activity determines fatigue resistance but does not affect maximal muscle force or contraction rates. We conclude that the opposing roles of SERCA activity and expression of ryanodine receptors in determining fatigue resistance and force production, respectively, at least partly explain differences in sprint and endurance performance in isolated rat gastrocnemius muscle.

Do Local Adaptation and the Reproductive Tactic of Atlantic Salmon (Salmo salarL.) Affect Offspring Metabolic Capacities?

Atlantic salmon (Salmo salar L.) is an iteroparous, anadromous species that exhibits some of the greatest within-population variability in size and age at maturity of all vertebrates. In the conditional reproductive strategy of salmonids, the male reproductive tactic expressed is believed to depend on an individual male's status relative to others in the population and therefore depends on his capacity to attain a physiological threshold, the exact nature of which is unknown. Although the threshold is influenced by local biotic and abiotic conditions, it is likely to be under genetic control. Our study examined whether the early growth, muscle metabolic capacities, routine metabolic rate, and spontaneous swimming of salmon alevins reared in laboratory conditions varied with the population of origin, maternal investment, and the paternal reproductive tactic. Our experimental design allowed us to establish that neither the population of origin nor the paternal reproductive tactic influenced the physiological capacities of alevins. The strong influence of the mother on alevin metabolic capacities suggests that the bioenergetic differences in metabolic capacities, realized metabolic rates, and activity levels that could eventually dictate the reproductive tactic of male offspring may originate in maternal effects.

Organochlorine Compounds and Their Metabolites in Seven Icelandic Seabird Species - a Comparative Study

The present study is designed to assess the occurrence of a few organochlorine contaminants and their metabolites in eggs of different marine bird species in Iceland, a country located in the sub-Arctic of the North-Western Atlantic. Previous investigations from e.g. Sweden and The Netherlands have shown some obvious differences in contaminant concentrations, including e.g. hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) in guillemot (Uria aalge) and other bird species. Eggs from seven marine bird species, Arctic tern (Sterna paradisaea), common eider (Somateria mollissima), guillemot, fulmar (Fulmarus glacialis), great black-backed gull (Larus marinus), lesser black-backed gull (Larus fuscus), and great skua (Stercorarius skua), that all breed in Iceland, were collected and analyzed for several persistent organic compounds and their metabolites. The contaminant levels varied between the species investigated. The highest concentrations were found in eggs from the great skua (18 and 23 microg/g l.w. of CB-153 and 4,4'-DDE, respectively). The concentration difference was generally 2 orders of magnitude higher in great skua for all organochlorine compounds analyzed with the exception of HCB. HCB did not vary as much between the seven species (ranging from 34 to 710 ng/g l.w). OH-PCB and MeSO(2)-PCB metabolites congener concentrations and patterns showed differences in metabolic capacity between bird species. Guillemot and great skua seem to distinguish themselves most from other species i.e. with the absence of 4-OH-CB187 and low relative levels of 4-OH-CB146 in guillemot and the low abundance of OH-PCBs in great skua.

Gender and species differences in triadimefon metabolism by rodent hepatic microsomes

Understanding the potential differences in metabolic capacity and kinetics between various common laboratory species as well as between genders is an important facet of chemical risk assessment that is often overlooked, particularly for chemicals which undergo non-cytochrome P450 mediated metabolism. The use of physiologically based pharmacokinetic (PBPK) models to better describe chemical exposure is made more powerful by incorporation of high quality in vitro kinetic data. To this end, metabolism of the conazole fungicide triadimefon was studied in hepatic microsomes of both genders of SD rats and CD-1 mice. Triadimefon depletion and triadimenol formation were measured in each type of microsomes. Michaelis–Menten regressions were applied to metabolic data and VMAX and the Michaelis constant (KM) values calculated. Male SD rats metabolized triadimefon more rapidly than female SD rats or either gender of CD-1 mouse. KM values were in the micromolar range, indicating the possibility of competitive inhibition with endogenous substrates. Intrinsic clearances derived from kinetic parameters indicate that triadimefon metabolism is blood-flow limited in all organisms studied with the possible exception of female rat. The in vitro half-life method was investigated as a less resource intensive method for the derivation of intrinsic clearance, and was found to be useful as a complement to the traditional Michaelis–Menten approach.

Evaluation of Time Dependence and Interindividual Differences in Benzo[a]pyrene-Mediated CYP1A1 Induction and Genotoxicity in Porcine Urinary Bladder Cell Cultures*

Exposure to tobacco smoke is an established cause of cancer in humans and cigarette smoking is a risk factor for urinary bladder cancer development. Aromatic amines are believed responsible for the bladder-specific carcinogenic effect, but polycyclic aromatic hydrocarbons (PAHs) are also of potential relevance. Urothelial cells contain a number of xenobiotic-metabolizing enzymes, which enable them to convert pro-carcinogens into reactive intermediates. In a preceding study, it was demonstrated using cultured porcine urinary bladder epithelial cells (PUBEC) that CYP1A1 mRNA is induced in a potent manner by treatment with benzo[a]pyrene (BaP). In the present study, the time dependence of these effects was evaluated and whether PUBEC cultures derived from individual donors respond differently to BaP treatment was determined. CYP1A1 induction was analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR), and genotoxic effects were studied using the Comet assay. Incubation of PUBEC with BaP increased CYP1A1 expression and induction of DNA strand breaks in a time-dependent manner. Interindividual differences were found between PUBEC cultures derived from several donor animals with respect to the response to BaP, such that the extent of CYP1A1 induction and magnitude of DNA damage was interrelated. Hence, individual differences in metabolic capacities and responsiveness to xenobiotics of urothelial cells from individual donors may be factors in susceptibility to genotoxic effects induced by PAHs.