Complex Polycyclic Aromatic Hydrocarbons Research Articles

Inhalation Cancer Risk Associated with Exposure to Complex Polycyclic Aromatic Hydrocarbon Mixtures in an Electronic Waste and Urban Area in South China

Atmospheric particulate matter samples were collected from May 2010 to April 2011 in a rural e-waste area and in Guangzhou, South China, to estimate the lifetime inhalation cancer risk from exposure to parent polycyclic aromatic hydrocarbons (PAHs), high molecular weight PAHs (MW 302 PAHs), and halogenated PAHs (HPAHs). Seasonal variations in the PAH concentrations and profiles within and between the e-waste and urban areas indicated different PAH sources in the two areas. Benzo[b]fluoranthene, benzo[a]pyrene, dibenz[ah]anthracene, and dibenzo[al]pyrene made the most significant contribution to the inhalation cancer risk. MW 302 PAHs accounted for 18.0% of the total cancer risk in the e-waste area and 13.6% in the urban area, while HPAHs made a minor contribution (<0.1%) in both the areas. The number of lifetime excess lung cancers due to exposure to parent PAHs, MW 302 PAHs, and HPAHs ranged from 15.1 to 1198 per million people in the e-waste area and from 9.3 to 737 per million people in Guangzhou. PAH exposure accounted for 0.02 to 1.94% of the total lung cancer cases in Guangzhou. On average, the inhalation cancer risk in the e-waste area was 1.6 times higher than in the urban area. The e-waste dismantling activities in South China led to higher inhalation cancer risk due to PAH exposure than the urban area.

Improved Separation of Complex Polycyclic Aromatic Hydrocarbon Mixtures Using Novel Column Combinations in GC × GC/ToF-MS

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are difficult to resolve because of the high degree of overlap in compound vapor pressures, boiling points, and mass spectral fragmentation patterns. The objective of this research was to improve the separation of complex PAH mixtures (including 97 different parent, alkyl-, nitro-, oxy-, thio-, chloro-, bromo-, and high molecular weight PAHs) using GC × GC/ToF-MS by maximizing the orthogonality of different GC column combinations and improving the separation of PAHs from the sample matrix interferences, including unresolved complex mixtures (UCM). Four different combinations of nonpolar, polar, liquid crystal, and nanostationary phase columns were tested. Each column combination was optimized and evaluated for orthogonality using a method based on conditional entropy that considers the quantitative peak distribution in the entire 2D space. Finally, an atmospheric particulate matter with diameter <2.5 μm (PM(2.5)) sample from Beijing, China, a soil sample from St. Maries Creosote Superfund Site, and a sediment sample from the Portland Harbor Superfund Site were analyzed for complex mixtures of PAHs. The highest chromatographic resolution, lowest synentropy, highest orthogonality, and lowest interference from UCM were achieved using a 10 m × 0.15 mm × 0.10 μm LC-50 liquid crystal column in the first dimension and a 1.2 m × 0.10 mm × 0.10 μm NSP-35 nanostationary phase column in the second dimension. In addition, the use of this column combination in GC × GC/ToF-MS resulted in significantly shorter analysis times (176 min) for complex PAH mixtures compared to 1D GC/MS (257 min), as well as potentially reduced sample preparation time.

Exposure time–dependent effects on the relative potencies and additivity of PAHs in the Ah receptor‐based H4IIE‐luc bioassay

In the present study, relative potency factors (REPs) of 16 individual polycyclic aromatic hydrocarbons (PAHs) were investigated using the H4IIE-luc bioassay. Exposure time-dependent effects on the REPs were examined using 24, 48, and 72 h of exposure. Seven different mixtures of PAHs were tested for additivity at an exposure time of 24 h. Three of the PAH mixtures were also studied at 48 and 72 h of exposure. The mixture toxicities were predicted using the REP concept and the concentration addition (CA) model. Relative potency factor values investigated in the present study were similar to those reported in earlier studies. Declining REPs with an increasing exposure time were shown for all PAHs, indicating that this bioassay approach could be developed to assess the persistency of aryl hydrocarbon receptor (AhR) agonistic PAHs and in the risk assessment of complex PAH mixtures. The results from the mixture studies indicated that additive interactions of PAHs are time dependent. Generally, 48- and 72-h exposures resulted in biological effects that were similar to the CA and REP model predictions, while these models tended to underestimate the effect, to some extent, in the 24-h exposure, at least for the mixtures containing two to four PAHs. Thus, it cannot be ruled out that in the 24-h exposures, the tested PAH mixtures had slight synergistic effects. Further research is needed to identify and test additional AhR activating PAHs and investigate whether the effects in the H4IIE-luc bioassay are additive for more complex samples containing both PAHs and other AhR-activating contaminants. Also, the observed superinduction of luciferase by PAH-mixes warrants studies of whether this also can occur for relevant AhR-mediated endpoints in vivo.

Characterization of pyrene utilizing Bacillus spp. from crude oil contaminated soil

Pyrene, a high molecular weight polycyclic aromatic hydrocarbon (PAH), is a priority pollutant present in soil contaminated with crude oil, coal-tar and complex PAHs. Bacterial consortium CON-3 developed from crude oil contaminated soil of Patiala, Punjab (India) cometabolized 50 μg ml-1 pyrene in the presence of glucose (0.5 %; w/v) at 30 °C, as determined by reverse-phase high performance liquid chromatography (HPLC). Bacillus sp. PK-12, Bacillus sp. PK-13 and Bacillus sp. PK-14 from CON-3, identified by 16S rRNA gene sequence analysis, were able to cometabolize 64 %, 55 % and 53 % of pyrene in 35 days, respectively. With the increase in glucose concentration to 1.0 % (w/v) in growth medium isolates PK-12, PK-13 and PK-14 showed 19 - 46 % uptake of 50 μg ml-1 pyrene in 4 days, respectively. Uptake of pyrene was correlated with growth and biosurfactant activity, which is suggestive of the potential role of members of Bacillus genera in pyrene mobilization and its uptake.

Environmental nitration processes enhance the mutagenic potency of aromatic compounds

This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2-Nitrophenol (2-NP), 2,4-Dinitrophenol (2,4-DNP), Pyrene (Py), 1-Nitropyrene (1-NPy), 1,3-Dinitropyrene (1,3-DNPy), 1,6-Dinitropyrene (1,6-DNPy), and 1,8-Dinitropyrene (1,8-DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1-NPy and 1,8-DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.

Environmental nitration processes enhance the mutagenic potency of aromatic compounds

This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2-Nitrophenol (2-NP), 2,4-Dinitrophenol (2,4-DNP), Pyrene (Py), 1-Nitropyrene (1-NPy), 1,3-Dinitropyrene (1,3-DNPy), 1,6-Dinitropyrene (1,6-DNPy), and 1,8-Dinitropyrene (1,8-DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1-NPy and 1,8-DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.

A novel approach for characterization of polycyclic aromatic hydrocarbon (PAH) pollution patterns in sediments from Guanabara Bay, Rio de Janeiro, Brazil

A novel multivariate method based on principal component analysis of pre-processed sections of chromatograms is used to characterize the complex PAH pollution patterns in sediments from Guanabara Bay, Brazil. Five distinct sources of 3- to 6-ring PAHs could be revealed. The harbour is the most contaminated site in the bay, its plume stretches in a South West to North East direction and the chemical profile indicates mainly pyrogenic sources mixed with a fraction of high-molecular-weight petrogenic PAHs. Rio São João de Meriti is the second largest source of PAHs, and introduces mainly a fraction of low-molecular-weight petrogenic PAHs from the western region of Rio de Janeiro. The sites close to the ruptured pipeline at the Duque de Caxias Refinery show a distinctive pollution pattern indicating a heavy petroleum fraction. The method also led to the identification of new potential indicator ratios also involving coeluting peaks (e.g., triphenylene and chrysene).

CO-exposure to mercury accelerates autoimmunity induced by trichloroethylene

Acute effects of individual and complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are well documented in vertebrate species. Hypoxia in fish reduces metabolic rate and reproduction. However, less is known about the later life consequences stemming from early-life exposure to PAHs or hypoxia, particularly their co-exposure. To address this, medaka (Oryzias latipes) embryos were exposed to a complex PAH mixture sediment extract from the Elizabeth River, VA (ERSE) at concentrations of 0.1, 0.5, or 1.0% or to one of three different hypoxia scenarios: continuous, nocturnal, or late stage embryogenesis hypoxia. Co-exposures with 0.1% ERSE and each of the hypoxia scenarios were conducted. Results included decreased survival with ERSE, hatching delays with hypoxia, and higher occurrences of deformities with each. The continuous hypoxia scenario caused the most significant changes in all endpoints. These early-life exposures altered later-life growth, impaired reproductive capacity, and reduced the quality of their offspring. ERSE alone resulted in a female-biased sex ratio while continuous or nocturnal hypoxia produced significantly greater numbers of males; and co-exposure produced an equal sex ratio. Exposure to a PAH mixture and hypoxia during early life stages has meaningful later-life and next generational consequences.

SAFFRON AS ENVIRONMENTAL BIOMARKER OF DIFFUSE CONTAMINATION

For the first time saffron has been employed as environmental bioindicator to characterize the presence of a complex polycyclic aromatic hydrocarbons (PAHs) mixture. The objective of this study was to provide quantitative information regarding PAHs contamination in saffron in order to verify the possibility to use this spice as environmental biomarker and to determine the bioaccumulation of these compounds. 27 saffron samples coming from different countries were analyzed by stir bar sorptive extraction technique in combination with gas chromatography-ion trap tandem mass spectrometry. The data show that the samples contained different levels of contaminants but some of them have higher concentrations than the maximum residue limits (MRLs) of pollutants established by the European Commission for spices. 9 out of 27 saffron samples contained benzo[a]pyrene in a range between 10.5 and 18.5 μg/kg values higher than the MRL.

Application of molecular fingerprinting for analysis of a PAH-contaminated soil microbiota growing in the presence of complex PAHs

Polycyclic aromatic hydrocarbons (PAHs) constitute a group of priority pollutants which are present at high concentrations in the soils of many industrial contaminated sites. Pollution by these compounds may stimulate growth of organisms able to live in these environments causing changes in the structure of the microbial community due to some cooperative process of metabolization of toxic compounds. A long-term PAH-contaminated soil was stored for several years and used to analyze the native microbiota regarding their ability to grow on pyrene, benzo[a]pyrene, as well as in mixtures of LMW- and HMW-PAHs. Molecular profiles of the microbial community was assessed by PCR-DGGE of 16S rRNA gene, and the number of bands observed in DGGE analyses was interpreted as dominant microbial members into the bacterial community. Results of PAH-contaminated soil microorganisms showed different profiles in the degradative dynamics when some nutrients were added. Predominant species may play a significative role while growing and surviving on PAHs, and some other metabolically active species have emerged to interact themselves in a cooperative catabolism of PAHs.

Mutagenic hazards of complex polycyclic aromatic hydrocarbon mixtures in contaminated soil

The objective of the present study was to evaluate hazard/risk assessment methods for complex environmental mixtures that involve a targeted, priority chemical approach based on the cumulative hazard/risk of known mixture components or analyses of sufficiently similar mixtures. Ten polycyclic aromatic hydrocarbon (PAH)-contaminated soils were separated into nonpolar and semipolar fractions, and both fractions elicited positive responses on the Salmonella reverse mutation assay. Targeted and nontargeted methods of hazard prediction routinely overestimated mutagenic activities for the nonpolar soil fractions, suggesting nonadditive interactions of PAHs in complex mixtures. This suggests that current risk assessment methods for complex mixtures may provide conservative estimates regarding soils contaminated with priority PAHs alone. Significant underestimations of total risk, however, will be obtained if the soils also contain unidentified PAHs as well as polycyclic aromatic compounds and related compounds that contribute to the total mutagenic activity. Furthermore, estimates of excess lifetime cancer risk associated with the nondietary ingestion of the PAH-contaminated soils studied here indicate that a traditional risk assessment model based on identified priority PAHs and an assumption of additivity generally underestimates the risk associated with the nonpolar soil fractions (in comparison to bioassay-derived risk estimates). Additional cancer risk may be associated with the more polar compounds that also are found at these contaminated sites and that rarely are included in the standard risk assessment methodology.

In situ biomonitoring of PAH-contaminated sediments using juvenile coho salmon ( Oncorhynchus kisutch)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous marine and freshwater sediment contaminants. Extensive data exist to confirm that PAHs are toxic to aquatic receptors. However, limited information is available regarding the bioavailability and genotoxicity of sediment PAHs to aquatic organisms. This study investigated an integrated biomonitoring approach using chemical analyses and biomarkers to characterize the bioavailability and genotoxicity of a complex PAH mixture in freshwater lake sediments associated with a former manufactured gas plant (MGP). Sediment PAH genotoxicity was assessed by flow cytometry (FCM), DNA adduct 32P-postlabeling, and erythrocyte micronuclei in juvenile coho salmon ( Oncorhynchus kisutch) caged in the water column. Significant PAH-induced genotoxicity was observed with FCM and 32P-postlabeling, but not with erythrocyte micronuclei. Chromosome damage in peripheral blood and hepatic DNA adducts correlated with sediment, but not water column PAH concentrations. Total hepatic DNA adducts in salmon caged nearest the former MGP facility was 39±6.5 (RAL×10 9), while salmon caged in a reference lake had 28±2.3 total hepatic DNA adducts per 10 9 nucleotides. These results indicate that in situ biomonitoring using biomarkers and caged fish can be a sensitive indicator of genotoxic PAHs in sediments.

Mineralization of PAHs in coal–tar impacted aquifer sediments and associated microbial community structure investigated with FISH

The microbial community structure and mineralization of polycyclic aromatic hydrocarbons (PAHs) in a coal–tar contaminated aquifer were investigated spatially using fluorescence in situ hybridization (FISH) and in laboratory-scale incubations of the aquifer sediments. DAPI-detected microbial populations in the contaminated sediments were three orders of magnitude greater than nearby uncontaminated sediments, suggesting growth on coal–tar constituents in situ. Actinobacteria, β- and γ- Proteobacteria, and Flavobacteria dominated the in situ aerobic (>1 mg l −1 dissolved oxygen) microbial community, whereas sulfate-reducing bacteria comprised 37% of the microbial community in the sulfidogenic region of the aquifer. Rapid mineralization of naphthalene and phenanthrene were observed in aerobic laboratory microcosms and resulted in significant enrichment of β- and γ- Proteobacteria potentially explaining their elevated presence in situ. Firmicutes, Flavobacteria, α- Proteobacteria, and Actinobacteria were also enriched in the mineralization assays, but to a lesser degree. Nitrate- and sulfate-limited mineralization of naphthalene in laboratory microcosms occurred to a small degree in aquifer sediments from locations where groundwater chemistry indicated nitrate- and sulfate-reduction, respectively. Some iron-limited mineralization of naphthalene and phenanthrene was also observed in sediments originating near groundwater measurements of elevated ferrous iron. The results of this study suggest that FISH may be a useful tool for providing a much needed link between laboratory microcosms and groundwater measurements made in situ necessary to better demonstrate the potential for natural attenuation at complex PAH contaminated sites.

Kinetics of biodegradation of binary and ternary mixtures of PAHs

The kinetics of biodegradation of mixtures of polycyclic aromatic hydrocarbons (PAHs) by Sphingomonas paucimobilis strain EPA505 were investigated. The investigation focused on three- and four-ring PAHs, specifically 2-methylphenanthrene, fluoranthene, and pyrene. Uptake rates in aerobic batch suspended cultivations were measured for the individual PAHs and their binary and ternary mixtures. It was observed that kinetics were influenced by the mixture composition and the kinetic properties of the components. A material balance equation containing the Monod model was numerically fitted to uptake data to determine extant kinetic parameters for the individual PAHs. Similarly, equations containing kinetic interaction models derived from enzyme kinetics were fitted to the uptake data obtained from experiments with binary and ternary mixtures. The investigation considered the following interaction types: no-interaction (Monod), pure competitive interaction, noncompetitive or mixed-type interaction, uncompetitive inhibition, and nonspecific interaction based on pure competition (SKIP). Model fit was evaluated based on probabilistic and statistical criteria and inferences were reached about underlying interaction mechanisms based on model fit. Mixture kinetics were most adequately simulated by the pure competitive interaction model with mutual substrate exclusivity. This model is fully predictive, relying only on parameters determined in the sole-PAH experiments. It was shown that for low percent inhibition values and with limited data, pure competitive interaction kinetics may not be evident, resembling no-interaction kinetics. This study is a reasonable starting point for understanding and modeling biodegradation of complex PAH mixtures in engineered and natural systems.

Evaluating Human Risk from Exposure to Alkylated PAHs in an Aquatic System

ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) are a large class of organic chemicals typically found as mixtures in the aquatic environment from natural, petrogenic, and pyrogenic sources. People can be exposed to PAHs through ingestion or dermal contact with contaminated sediments or through ingestion of finfish and shellfish exposed to contaminated sediments. Although more than 100 PAHs have been identified, human exposure and risk are commonly evaluated for 18 individual PAHs. Other PAHs, such as alkylated PAHs, likely contribute to biological activity of environmental PAH mixtures; however, insufficient toxicity data are available to quantify their potential risk. This article presents an initial evaluation of the potential for human health risk from exposure to alkylated PAHs in sediment and fish. Individual alkylated PAHs have been observed to have potentially mutagenic, tumor-promoting, or carcinogenic activity. However, except for 1-and 2-methylnaphthalene, insufficient toxicity data are available to quantify toxicity or cancer risk from exposure to individual alkylated PAHs or mixtures of alkylated PAHs. This article describes a proposed strategy to better understand the potential human health risk from exposure to alkylated PAHs. Implementation of this strategy will contribute to evaluations of human exposure to complex PAH mixtures in the environment.

Mutagenic Hazards of Complex Polycyclic Aromatic Hydrocarbon Mixtures in Contaminated Soil

Mutagenic Hazards of Complex Polycyclic Aromatic Hydrocarbon Mixtures in Contaminated Soil

Competitive inhibition of carcinogen‐activating CYP1A1 and CYP1B1 enzymes by a standardized complex mixture of PAH extracted from coal tar

A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, the Standard Reference Material (SRM) 1597, was recently shown to decrease the levels of DNA binding of the 2 strong carcinogens benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) in the human mammary carcinoma-derived cell line MCF-7 (Mahadevan et al., Chem Res Toxicol 2005;18:224-231). The present study was designed to further elucidate the biochemical mechanisms involved in this inhibition process. We examined the effects of SRM 1597 on the metabolic activation of BP and DBP toward DNA-binding derivatives in Chinese hamster cells expressing either human cytochrome P450 (CYP) 1A1 or CYP1B1. SRM 1597 inhibited BP-DNA adduct formation through the entire exposure time in cells expressing human CYP1A1, while it significantly inhibited adduct formation only up to 48 hr when co-treated with DBP. Conversely, human CYP1B1-expressing cells were unable to catalyze PAH-DNA adduct formation on treatment with SRM 1597 alone, and on co-treatment with BP or DBP. The data obtained from biochemical experiments revealed that SRM 1597 competitively inhibited the activity of both human enzymes as analyzed by 7-ethoxyresorufin O-deethylation assays. While the Michaelis-Menten constant (K(M)) was <0.4 microM in the absence of SRM 1597, this value increased up to 1.12 (CYP1A1) or 4.45 microM (CYP1B1) in the presence of 0.1 microg/ml SRM 1597. Hence the inhibitory effects of the complex mixture on human CYP1B1 were much stronger when compared to human CYP1A1. Taken together, the decreases in PAH-DNA adduct formation on co-treatment with SRM 1597 revealed inhibitory effects on the CYP enzymes that convert carcinogenic PAH into DNA-binding metabolites. The implications for the tumorigenicity of complex environmental PAH mixtures are discussed.

Contribution of domestic effluents to hydrocarbon levels of dry weather flow in combined sewers

The importance of hydrocarbon contamination of the sewer network has been reported by many authors recently. Most of the studies are focused on the introduction of such pollutants into combined sewers by street and roof stormwater, but few evaluate the contribution of domestic inputs to hydrocarbon pollution. As a consequence, this work—carried out on the framework of the OPUR (Observatory of Urban Pollutants) research program—assesses the resolved aliphatic (AH), unresolved complex mixture (UCM) and polycyclic aromatic hydrocarbon (PAH) concentrations of domestic effluents (DE) and evaluates the role played by such effluents on the hydrocarbon levels of dry weather flow (DWF) in combined sewers. Results show hydrocarbon concentrations in the 200 – 300 μg · l−1, 300 – 1 000 μg · l−1 and 0.9 – 1.4 μg · l−1 ranges for AHs, UCM and the 16 PAHs of the US-EPA, respectively. The assessment of hydrocarbon fluxes conveyed by domestic effluents on the scale of the ‘Le Marais’ experimental urban catchment (42 ha, centre of Paris) reveals the predominant contribution of domestic inputs to the DWF pollution and highlights the unsuspected role of households.

Characterization and classification of complex PAH samples using GC–qMS and GC–TOFMS

The aim of this study was to compare the polycyclic aromatic hydrocarbon (PAH) contents in a number of complex samples, including soil samples from industrial sites, anti-skid sand, urban dust and ash samples from municipal solid waste incinerators. The samples were characterized by routine analysis of PAHs (gas chromatography–quadrupole mass spectrometry) and gas chromatography–time of flight mass spectrometry (GC–TOFMS). Classification of the samples by principal component analysis (PCA) according to their composition of PAHs revealed that samples associated with traffic and the municipal incinerator formed homogeneous clusters, while the PAH-contaminated soils clustered in separate groups. Using spectral data to resolve co-eluting chromatographic peaks, 962 peaks could be identified in the GC–TOFMS analysis of a pooled sample and 123–527 peaks in the individual samples. Many of the studied extracts included a unique set of chemicals, indicating that they had a much more diverse contamination profile than their PAH contents suggested. Compared to routine analysis, GC–TOFMS provided more detailed information about each sample and in this study a large number of alkylated PAHs were found to be associated with the corresponding unsubstituted PAHs. The possibility to filter peaks according to different criteria (e.g. to include only peaks that were detected in the analysis of another sample) was explored and used to identify unique as well as common compounds within samples. This procedure could prove to be valuable for obtaining relevant chemical data for use in conjunction with results from various biological test systems.

Inhibition of Human Cytochrome P450 1A1-, 1A2-, and 1B1-Mediated Activation of Procarcinogens to Genotoxic Metabolites by Polycyclic Aromatic Hydrocarbons

Many chemicals in the environment can cause cancer, and polycyclic aromatic hydrocarbons (PAHs) are among the most ubiquitous. Cancer risk assessments require consideration of these in complex mixtures. PAHs require metabolic activation by cytochrome P450 (P450) enzymes, primarily 1A1, 1A2, and 1B1. We determined if individual PAHs and other procarcinogens affect the activities of human P450s 1A1, 1A2, and 1B1 by measuring 7-ethoxyresorufin O-deethylation (EROD) activity and metabolic activation of PAH dihydrodiols and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline (MeIQ) to genotoxic metabolites in a Salmonella typhimurium NM2009 system. Of 23 PAHs examined, benz[a]anthracene (B[a]A), benzo[b]fluoranthene, and 5-methylchrysene were the most potent inhibitors of P450 1A2- and 1B1-catalyzed EROD activity, with IC50 values <10 nM. Other PAHs, e.g., dibenz[a,c]anthracene, dibenz[a,h]anthracene, dibenz[a,j]acridine, and 3-methylcholanthrene, rather selectively inhibited P450 1B1, with IC50 values <15 nM. Benzo[a]pyrene (B[a]P) and nine other PAHs also inhibited P450 1A2 as well as 1B1 with IC50 values <150 nM. Parent PAH compounds were generally more potent than 10 dihydrodiol metabolites of PAHs and 3- and 9-hydroxy B[a]P in inhibiting EROD activity. In addition, we found that three selected PAHs (5-methylchrysene, B[a]P, and B[a]A) inhibited metabolic activation of 5-methylchrysene-1,2-diol, (+/-)-B[a]P-7,8-diol, dibenzo[a,l]pyrene-11,12-diol, and MeIQ to genotoxic metabolites catalyzed by P450s 1A1, 1B1, and 1A2, respectively, in S. typhimurium NM2009. Thus, individual PAHs may affect their own and metabolism of other carcinogens catalyzed by P450 1A1, 1A2, and 1B1, and these phenomena cause alteration in their ability to transform cells when single or complex PAH mixtures are ingested by mammals, influencing risk assessment.