Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complex Mixtures”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2006

In vitro models for assessing neurotoxicity of mixtures.

Rapid and inexpensive methods are needed to investigate the interactions of complex mixtures. This commentary addresses the use of cell cultures to detect neurotoxicity of simple binary mixtures, which is a first step in the development of such methods. A small number of recent studies from our laboratory are examined. Though such studies are few, they offer guidance for optimizing the value of cell cultures as systems for chemical toxicity screening and mechanistic research. The same issues that apply to in vitro neurotoxicity studies of single agents also apply to the study of mixtures, such as relevance of endpoints tested, biological usefulness and limitations of cell culture models, and relevance of exposures tested. In this commentary we will focus on several aspects of these issues.

Animals↗
PubMed2004

Oxidative activation of the human carcinogen chromate by arsenite: a model for synergistic metal activation leading to oxidative DNA damage.

Human exposure to toxic metals and metalloids in the environment seldom occurs from a single pure compound. Most environmental exposure profiles are heterogeneous with co-exposure occurring coincident with multiple toxic metal species. This co-exposure to metals and metalloids in complex mixtures can result in a synergistic, additive or even depletive toxic response. The complexity of interactions presented by metal mixtures presents a need for convenient and sensitive methods to determine potential toxic responses from such co-exposure. We have studied the reaction between the two commonly associated toxic metals of chromate, Cr(VI), and arsenite, As(III), with regards to the ability of As(III) to reductively activate Cr(VI) to generate oxidative stress and DNA damage. Using a DCF-based fluorescent dye assay we have demonstrated that the redox reaction between As(III) and Cr(VI) yields high valent intermediates of chromium, Cr(V), that are highly oxidizing. This induction of oxidizing potential was dose dependent and did not occur with As(III) or Cr(VI) alone or, with the other major oxidation state of arsenic, arsenate, As(V). The mechanism of oxidation of DCFH to the fluorescent species, DCF, in this reaction was through a direct, metal-based oxidation since addition of radical scavengers did not significantly decrease oxidation of the dye in this system. The addition of a ligand that stabilizes the high valent Cr(V) oxidation state, 2-ethyl-2-hydroxybutyric acid (EHBA), to the chromate and arsenite mixture resulted in an enhancement of DCF fluorescence. The DCF fluorescence observed with the Cr(VI) and As(III) mixture was also found to correlate with oxidative DNA damage as measured by a plasmid nicking assay. These data show how metal-metal interactions in environmental mixtures could result in the synergistic induction of oxidative stress and DNA damage. Further, these data demonstrate the utility of the DCF fluorescence assay as a sensitive method for screening synergistic redox interactions in metal mixtures.

Arsenites↗
PubMed1983

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity.

Metallic elements contained in coal, oil and gasoline are mobilized by combustion processes and may be emitted into the atmosphere, mainly as components of submicron particles. The information about the amounts, composition and form of metal compounds is reviewed for some fuels and combustion processes. Since metal compounds are always contained in urban air pollutants, they have to be considered whenever an evaluation of biological impact of air pollutants is made. The value of currently used bioassays for the evaluation of the role of trace metal compounds, either as major biologically active components or as modifiers of biological effects of organic compounds is assessed. The whole animal bioassays for carcinogenicity do not seem to be an appropriate approach. They are costly, time-consuming and not easily amenable to the testing of complex mixtures. Some problems related to the application and interpretation of short-term bioassays are considered, and the usefulness of such bioassays for the evaluation of trace metal components contained in complex air pollution mixtures is examined.

Air Pollutants↗
PubMedDate not supplied

Targeted proteomics of low-level proteins in human plasma by LC/MSn: using human growth hormone as a model system.

This paper describes the profiling of human growth hormone (hGH) in human plasma in order to assess the dynamic range of the ion-trap mass spectrometer for proteomic studies of complex biological samples. Human growth hormone is an example of a low-level plasma protein in vivo, present at subfemtomole levels. This study was performed on a plasma sample in which hGH has been spiked at 10-fold above the natural level, that is approximately 16 pg/microL of plasma. Initially, the measurement was carried out without any sample enrichment and consisted of the following steps: the full set of plasma proteins were reduced, alkylated, and digested with trypsin, and the resulting peptides were separated on a capillary C-18 column and then detected by ion-trap mass spectrometry (1D LC/MS). In addition, this study provided a global view of the serum proteome with over 200 plasma proteins being preliminarily identified. In the MS/MS analysis, hGH was detected by characterization of the first tryptic peptide (T1). The initial identification was confirmed by alternative approaches, which also allowed the evaluation of different sample purification protocols. First, the plasma sample containing hGH was fractionated on a reversed-phase HPLC column and digested, and hGH could now be identified by MS/MS measurements of two tryptic peptides (T1 and T4) by the same 1D LC/MS protocol. In addition, the assignment of peptide identity was made with higher certainty (as measured by an algorithm score). The plasma sample was also fractionated by 1D and 2D gel electrophoresis, the selected bands were digested and analyzed again by the 1D LC/MS protocol. In both cases using the gel prepurifications, hGH was identified with additional peptides. Finally, the plasma sample was analyzed by 2D chromatography (ion exchange and reversed phase) on a new instrumental platform (ProteomeX), and hGH was identified by the observation of five tryptic peptides. In conclusion, these experiments were able to detect growth hormone in the low femtomole level with a dynamic range of 1 in 40 000 by several independent approaches. The amount of growth hormone, while 10-fold above normal in vivo levels, represents concentrations that may be present in disease states (such as acromegaly) and also in doping control measurements. These studies have demonstrated that shotgun sequencing approaches (LC/MS/MS) not only can profile high-abundance proteins in complex biological fluids but also have the potential to identify and quantitate low-level proteins present in such complex mixtures without extensive prepurification protocols. A key to such studies, however, is to use targeted approaches that reduce the complexity of the solute mixture that is presented to the mass spectrometer at a given time point. The various sample preparation protocols described here all improved the quality of the hGH measurement, although in this study the 2D chromatographic approach gave the greatest sequence coverage.

Calibration↗
PubMed1987

Strategy for the analysis of steryl esters from plant and animal tissues.

Methods are described for the analysis of intact steryl esters present in complex mixtures isolated from plant or animal tissues. A preliminary examination by analytical thin-layer chromatography (TLC) and capillary column gas chromatography-mass spectrometry (GC-MS) under electron impact (EI) ionisation reveals the complexity of the mixture and the nature of the steryl moieties. Preparative TLC is then utilised to separate the steryl esters into two broad groups, containing fatty acyl moieties of shorter (C2-C8) or longer chain length (C10-C22). The shorter-chain fatty acyl steryl esters are separated by adsorption high-performance liquid chromatography (HPLC) on a LiChrosorb Silica-60 column. The steryl esters with longer-chain fatty acyl moieties are analysed by reversed-phase HPLC on either an Ultrasphere ODS, 5-micron, or a S3 Spherisorb ODS, 3-micron, column. Steryl esters with unsaturated fatty acyl moieties are eluted with the shorter-chain fatty acyl steryl esters. The presence of the unsaturated fatty acyl esters can be monitored by analytical argentation TLC, which will also reveal the degree of unsaturation. The steryl esters are fractionated into the saturated, mono-, di-, tri- and polyene acyl types by preparative medium-pressure liquid chromatography on a column of 10% AgNO3-silica gel. Each of these steryl ester types can then be resubmitted to reversed-phase HPLC or analysed by GC-MS on a short fused-silica capillary column with a bonded phase of the OV-1 type. GC-MS on a magnetic-sector instrument under negative-ion chemical ionisation conditions with ammonia as the reagent gas produces fragment ions for both the steryl and fatty acyl moieties, thus permitting identification of the individual intact steryl esters. These various methods are illustrated by analyses of the steryl ester mixtures obtained from human plasma, barley seedlings, palm oil and rape seed oil.

Animals↗
PubMed2004

Issues that must be addressed for risk assessment of mixed exposures: the U.S. EPA experience with air quality.

Humans are routinely exposed to a complex mixture of air pollutants in both their outdoor and indoor environments. The wide diversity of these exposure scenarios and potential for regional transport present the health scientist with a challenge of how to appropriately address complex air pollution mixtures. Similarly, regulators are faced with mixture issues ranging from exposures, to health outcomes, and to associated uncertainties that are in need of more definitive and strategic information to support informed decisions. This article provides a perspective of an empiricist on the background related to the issue of air pollution mixtures. Historic and current regulatory platforms for dealing with mixtures are described. Using the topic of particulate air pollution, general guidance through the nuances of potential interactions among PM constituents is provided, along with alterative approaches and examples, and how these support scientific and regulatory agendas. The impact of new cell and molecular technologies is inevitable, and we must be prepared to take advantage of these and other cross-cutting methods as they become available. Such innovative approaches hold the secret to high-throughput biologic dissection of component interactions and mixture profiles, which will aid in the assessment of risk.

Air Pollutants↗
PubMedDate not supplied

Toxicological characterisation of sludge from sewage treatment plants using toxicity identification evaluation protocols based on in vitro toxicity tests.

The ecotoxicological characterisation of complex mixtures, such as sludge from sewage treatment plants, is complex. Toxicity identification evaluation (TIE) protocols, developed by the United States Environmental Protection Agency (US EPA); to identify toxic pollutants in complex effluents, are useful tools in this context; to solve the difficulties in assessing unknown organic pollutants by analytical methods, the usefulness of bioassays to detect the relevant (toxic) organic compounds present in complex samples, and the possibilities of in vitro cytotoxicity tests as screening tools, offers a profitable combination. The sludge obtained from a sewage treatment plant was extracted by acetonitrile using a microwave extractor and fractionated in an HPLC system. The toxicity of every fraction was assayed using a RTG-2 cytotoxicty test, based on the fibroblastic RTG-2 fish cell line (ATCC, CCL N. 55). At exponential growth, three endpoints, beta-galactosidase activity, culture viability assayed by the neutral red assay (NR) and inhibition of growth rate using the FRAME KB protein assay (KBP), were used. By plotting the toxicity of each fraction vs elution time, the corresponding "toxicograms" were built. The UV and fluorescence chromatograms are compared to the three toxicograms (one for each toxicity endpoint).

Animal Testing Alternatives↗
PubMedDate not supplied

Enzymatic defluorination and metabolism of fluoroacetate, fluoroacetamide, fluoroethanol, and (-)-erythro-fluorocitrate in rats and mice examined by 19F and 13C NMR.

Fluoroacetate administered intraperitoneally (ip) to rats and mice is defluorinated to give fluoride ion evident in urine and kidney by 19F NMR. The use of [2-13C]-, [1,2-13C]-, and [1,2-14C]fluoroacetate, prepared from isotopically labeled glycine, combined with 13C NMR and TLC radioautography, respectively, reveals a complex mixture of urinary metabolites including an S-(carboxymethyl) conjugate complex in rats and mice and sulfoxidation products thereof in rats. Direct 13C NMR examination of the bile following treatment with [2-13C]fluoroacetate shows the presence of S-(carboxymethyl)glutathione or a related conjugate and an O-conjugate of fluoroacetate. Incubation of [13C]fluoroacetate with rat and mouse liver cytosol involves formation of S-[( 13C]carboxymethyl)glutathione and fluoride ion. Fluorocitrate is also detected by 19F NMR examination of fluoroacetate incubations with mouse liver cytosol. Fluoroacetamide administered ip to rats and mice yields urinary fluoride ion formed via fluoroacetate which is liberated on hydrolysis by an organophosphate-sensitive amidase. 19F NMR chemical shifts of other metabolites of fluoroacetamide are consistent with fluoroacetohydroxamic acid in the liver of mice and fluorocitrate in the urine of rats. Fluoroethanol gives urinary fluoroacetate and fluoride ion in rats and mice and is converted to fluoroacetaldehyde by mouse and rat liver microsomes. (-)- and (+)-erythro-fluorocitrates administered ip to rats yield mostly the parent compounds in urine at 6 h with increasing amounts of fluoride ion thereafter. 19F NMR establishes that rat and mouse liver cytosols defluorinate (-)- but not (+)-erythro-fluorocitrate and pig heart aconitase also defluorinates (-)-erythro-fluorocitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aconitate Hydratase↗
PubMed1986

The role of narrowly tuned taste cell populations in lobster (Homarus americanus) feeding behavior.

A whole-animal behavioral assay was developed to measure responses to chemical stimulation of the walking leg (taste) receptors of lobsters. Lesions of only the taste receptors abolished the dactyl clasping response, a result demonstrating that such receptors are necessary to elicit this response. Then the stimulatory effectiveness of natural and synthetic mixtures was determined, particularly of 6 single compounds (glutamate, glutamine, NH4Cl, betaine, aspartate, and taurine) for which the legs have prominent, narrowly tuned receptor cell populations. The results showed that a synthetic mixture of the 22 principal amino acids and amines present in mussel tissue is as powerful a stimulus as either a homogenate of such tissue or its purified extract. Of the single compounds, only NH4Cl was stimulatory at the behavioral level; glutamate was not despite the fact that glutamate receptors are the predominant cell population known in lobster legs. Even a mixture of the 6 single compounds in their natural mixture ratio was not very stimulatory (it was even less stimulatory than the sum of the responses to each single compound), a result suggesting the occurrence of suppressive interactions. The complementary mixture, that is, the synthetic mixture without the 6 single compounds, was equally unstimulatory. It is unlikely that mixture suppression alone is responsible for the poor behavioral responses to single compounds such as glutamate, and to the partial mixtures that were tested. Full response to the more complex mixture of 22 compounds demonstrates that special mixture combinations can "override" mixture suppression. Such signal mixtures may represent the lobster leg's picture of food.

Animals↗
PubMed1984

A functional assay of protein C in human plasma.

A three-step spectrophotometric assay was developed for measuring functional protein C (PC) in human plasma. The assay is based on: (1) adsorption of citrated platelet-poor plasma on barium citrate and elution of the vitamin K-dependent factors with EDTA; (2) activation of PC by incubation of the mixture of vitamin K-dependent factors with a complex of thrombin and its endothelial cell cofactor, thrombomodulin; (3) addition of antithrombin III and heparin to the system to inhibit thrombin and other coagulation enzymes generated during incubation and measurement of the activated PC with a synthetic (chromogenic) substrate. The assay appears to be specific for PC because: (a) PC-depleted plasma (by immunoadsorption) is inactive; (b) addition of purified PC to PC-depleted plasma reconstitutes its activity; and (c) no enzymatic activity is generated in the absence of the thrombin-thrombomodulin complex. Mixtures of a normal plasma pool with PC-depleted plasma yielded an amount of enzymatic activity proportional to the fraction of normal plasma. Using this as a standard curve, the amount of PC in the plasma of 23 normal subjects was 97% +/- 15%. The within-assay coefficient of variation was 3.5% and the between-assay coefficient 6.5%. A linear correlation (r = 0.86) was found between PC as measured with the functional assay and with a radioimmunoassay. In 3 patients with congenital PC deficiency, the functional PC level was 37% +/- 9% and the antigen level 64% +/- 11%. It is concluded that the present assay may be used for reliable and accurate estimation of activatable PC in human plasma.

Adsorption↗
PubMed1982

Application of the nitrocellulose transfer technique and alkaline phosphatase conjugated anti-immunoglobulin for determination of the specificity of monoclonal antibodies to protein mixtures.

The target antigens of a series of monoclonal antibodies raised against a complex mixture of proteins have been identified. The protein mixture was fractionated by polyacrylamide gel electrophoresis in SDS, and the fractionated proteins electrophoretically transferred to nitrocellulose sheets. Protein bands reacting with antibody were identified by incubating the nitrocellulose strips with the 'hybridoma' culture supernatants, followed by detection of bound antibody using alkaline phosphatase conjugated to rabbit anti-mouse F(ab')2 antibody, and histochemical substrates. With this technique, the antigens reacting with 4 of a series of 5 monoclonal antibodies have been identified.

Alkaline Phosphatase↗
PubMed1996

Kinetics of the simultaneous utilization of sugar mixtures by Escherichia coli in continuous culture.

In natural environments heterotrophic microorganisms encounter complex mixtures of carbon sources, each of which is present at a concentration of a few micrograms per liter or even less. Under such conditions no significant growth would be expected if cells utilized only one of the available carbon compounds, as suggested by the principle of diauxic growth. Indeed, there is much evidence that microbial cells utilize many carbon compounds simultaneously. Whereas the kinetics of single-substrate and diauxic growth are well understood, little is known about how microbial growth rates depend on the concentrations of several simultaneously utilized carbon sources. In this study this question was answered for carbon-limited chemostat growth of Escherichia coli fed with mixtures of up to six sugars; the sugars used were glucose, galactose, maltose, ribose, arabinose, and fructose. Independent of the mixture composition and dilution rate tested, E. coli utilized all sugars simultaneously. Compared with growth with a single sugar at a particular growth rate, the steady-state concentrations were consistently lower during simultaneous utilization of mixtures of sugars. The steady-state concentrations of particular sugars depended approximately linearly on their contributions to the total carbon consumption rate of the culture. Our experimental data demonstrate that the simultaneous utilization of mixtures of carbon sources enables heterotrophic microbes to grow relatively fast even in the presence of low environmental substrate concentrations. We propose that the observed reductions in the steady-state concentrations of individual carbon sources during simultaneous utilization of mixtures of carbon sources by heterotrophic microorganisms reflect a general kinetic principle.

Carbohydrate Metabolism↗
PubMed2002

Toxicological evaluation of chemical mixtures.

This paper addresses major developments in the safety evaluation of chemical mixtures during the past 15 years, reviews today's state of the art of mixture toxicology, and discusses challenges ahead. Well-thought-out tailor-made mechanistic and empirical designs for studying the toxicity of mixtures have gradually substituted trial-and-error approaches, improving the insight into the testability of joint action and interaction of constituents of mixtures. The acquired knowledge has successfully been used to evaluate the safety of combined exposures and complex mixtures such as, for example, the atmosphere at hazardous waste sites, drinking water disinfection by-products, natural flavouring complexes, and the combined intake of food additives. To consolidate the scientific foundation of mixture toxicology, studies are in progress to revisit the biological concepts and mathematics underlying formulas for low-dose extrapolation and risk assessment of chemical mixtures. Conspicuous developments include the production of new computer programs applicable to mixture research (CombiTool, BioMol, Reaction Network Modelling), the application of functional genomics and proteomics to mixture studies, the use of nano-optochemical sensors for in vivo imaging of physiological processes in cells, and the application of optical sensor micro- and nano-arrays for complex sample analysis. Clearly, the input of theoretical biologists, biomathematicians and bioengineers in mixture toxicology is essential for the development of this challenging branch of toxicology into a scientific subdiscipline of full value.

Air Pollutants↗
PubMed2006

Lability of a mixture of metal complexes under steady-state planar diffusion in a finite domain.

The rigorous analytical solution for the fluxes from a mixture of 1:1 metal complexes toward an active surface under steady-state planar diffusion in a finite domain and excess ligand conditions allows for the computation of the global degree of lability of the system as well as particular degrees of lability of each complex in the mixture. This kind of system is found in a variety of fields ranging from electrochemical techniques (such as stripping chronopotentiometry at scanned deposition potential, SSCP) to analytical devices (such as diffusion gradients in thin-film gels, DGT). Among the specific effects arising from the presence of a mixture of ligands competing for the metal we highlight the following: (i) The degree of lability of a complex in the mixture differs from its degree of lability in an unmixed system with the same ligand concentration, and (ii) the degree of lability of one complex depends on (i.e., can be modified with) the concentrations of the ligands in the mixture. The impact of these characteristics on the metal flux crossing the active surface reaches the highest value when both complexes are partially labile. The complex contribution to the metal flux goes through a maximum when the thickness of the diffusion domain is varied. Thus, the thickness of the diffusion domain can be chosen to enhance the contribution of one particular complex. Lability criteria for each complex of the mixture within the reaction layer approximation are also reported. In particular, the reaction layer formulation for a complex is discussed in detail for two limiting cases: the rest of complexes are all nonlabile or the rest of complexes are all labile.

Journal Article↗
PubMedDate not supplied

Capture of peptides with N-terminal serine and threonine: a sequence-specific chemical method for Peptide mixture simplification.

The objective of this study was to evaluate a sequence-specific chemistry for the ability to specifically capture peptides that contain N-terminal serine or threonine residues from mixtures. The first step is the oxidation of the 1,2-amino alcohol structure -CH(NH(2))CH(OH)- of peptides containing N-terminal serine or threonine with periodate. The newly formed aldehyde reacts with a labeling reagent containing a hydrazide, RCONHNH(2), to form a hydrazone-peptide conjugate, RCONHN=CH-peptide. Biotin-labeled conjugates can then be isolated by affinity purification with streptavidin. The method described in this report can be useful in simplifying the complex mixtures of peptides that are generated in typical proteomic analysis, where proteins are digested with trypsin and analyzed using liquid chromatography mass spectrometry data. The sequence-specific peptide selection not only reduces the complexity of digest mixtures, but also provides additional information for peptide identification. The targeted peptides are those that have either serine or threonine adjacent to a protease cleavage site. The sequence information should greatly aid in both database matching for protein identification and for de novo sequence determination.

Affinity Labels↗
PubMed1998

Kinetic models for the growth of Escherichia coli with mixtures of sugars under carbon-limited conditions.

In natural environments, heterotrophic microorganisms encounter complex mixtures of carbon sources, each of which is present only at very low concentrations. Under such conditions no significant growth could be expected if cells utilized only one of the available carbon compounds as suggested by the principle of diauxic growth. Indeed, there is much evidence that microbial cells utilize many carbon sources simultaneously. In order to predict bacterial growth under such conditions we developed a model describing the specific growth rate as a function of the individual concentrations of several simultaneously utilized carbon substrates. Together with multisubstrate models previously published, this model was evaluated for its ability to describe growth of Escherichia coli during the simultaneous utilization of mixtures of sugars in carbon-limited continuous culture. Using the micromax and Ks constants determined for single substrate growth with six different sugars, the model was able for most experiments to adequately describe the specific growth rate of the culture, i.e., the experimentally set dilution rate, from the measured concentrations of the individual sugars. The model provides an explanation why bacteria can still grow relatively fast under environmental conditions where the concentrations of carbon substrates are usually extremely low.

Culture Media↗
PubMed1985

Estimating the mass of mutagens in indeterminate mixtures.

A method is shown for estimating the quantity (mass) of genotoxic compounds in complex mixtures without prior identification of components. This method uses fractiles of the probability distribution of responses from the assay of interest and dose-response of the mixture. The method depends upon the assumption of additivity, on average, in the interaction of mutagens and on lognormality of the distribution of mutagen molecular weights. Mass estimates are necessary for hazard characterization, risk estimation, and risk assessment. The method is illustrated using Ames assay results from a coke plant wastewater.

Coke↗
PubMed1993

Synergistic activity of polynuclear aromatic hydrocarbon mixtures as aryl hydrocarbon (Ah) receptor agonists.

The relative potencies of benzo[a]pyrene and a complex mixture of polynuclear aromatic hydrocarbons (PAHs) produced as by-products of manufactured gas plant (MGP) residues as inducers of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity were determined in the B6C3F1 mouse. The ED50 values for the induction response were 78 and 65 mg/kg for benzo[a]pyrene and the MGP-PAH mixture, respectively. Analysis of the MGP-PAH mixture indicated that benzo[a]pyrene and other compounds containing four or more rings and which are known to induce EROD activity were only present as trace components of this mixture. A comparison of the EROD induction potencies of benzo[a]pyrene and the MGP-PAH mixture showed that the mixture was approximately 706 times more potent than expected based on its benzo[a]pyrene content (0.17%). This induced P-450 activity could significantly increase the metabolism of the carcinogenic PAHs and thereby modulate the overall carcinogenicity of the mixture. The apparent synergistic activity of the MGP-PAH mixture was further investigated by comparing the activities of this mixture and benzo[a]pyrene for several other aryl hydrocarbon (Ah) receptor-mediated responses including (i) induction of hepatic CYP1A1 mRNA levels, (ii) transformation of the rat cytosolic Ah receptor to a complex which binds to a dioxin responsive element, (iii) induction of EROD activity and (iv) antiestrogenicity in MCF-7 human breast cancer cells, and (v) inhibition of the splenic plaque-forming cell (PFC) response to both T cell-dependent and independent antigens in B6C3F1 mice. For the EROD and CYP1A1 mRNA induction and cytosolic transformation activities and immunosuppressive effects, the MGP-PAH mixture was approximately 100-900 times more potent as an Ah receptor agonist than expected based on its benzo[a]pyrene content. The synergistic activity was lower (19-fold) for the antiestrogenic response in MCF-7 cells. The reason for the synergistic effects of the MGP-PAH mixture were not due to contamination of the mixture by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds and the results suggest that the enhanced potency of the mixture is due to unknown interactions between the individual PAHs present in the mixture.

Animals↗