Class Of Polycyclic Aromatic Hydrocarbons Research Articles

Genotoxic substances in the St. Lawrence system I: Industrial genotoxins sorbed to particulate matter in the St. Lawrence, St. Maurice, and Saguenay rivers, Canada

AbstractPrevious investigations of organic genotoxins in industrial effluents discharged into the St. Lawrence Rivers system (Quebec, Canada) indicated that a substantial fraction of the genotoxicity is adsorbed to suspended particulate matter. This study used the SOS Chromotest to investigate the presence, potency, and behavior of particle‐bound genotoxins in the downstream ecosystem. The results indicate that although extracts of both suspended and sedimented particulate matter are genotoxic, suspended particulate matter samples are more potent in the absence of S9 activation, with the reverse being true for bottom sediments. The results confirmed a positive relationship between the genotoxicity of bottom sediment extracts and sediment organic matter content. A similar relationship between organic matter content and total polycyclic aromatic hydrocarbon (PAH) concentration indicates that putative genotoxins have physicochemical properties similar to the PAH class of contaminants. Conversion of PAH values to benzo[a]pyrene equivalents indicates that measured PAHs only account for a small fraction (∼10%) of the observed SOS Chromotest response. Sites that receive discharges from foundries, aluminum refineries, and petroleum refineries yielded several of the most genotoxic samples. Further analyses revealed that the genotoxicity of suspended and sedimented particulate matter extracts is empirically related to the genotoxicity of industrial discharges. Comparisons of total genotoxicity levels in suspended particulates and bottom sediments suggest that direct‐acting substances adsorbed to suspended matter are rapidly degraded and/or converted to more stable progenotoxins upon deposition. Further research is required to test this hypothesis and investigate effects on indigenous biota.

Formation and repair of DNA lesions in the p53 gene: relation to cancer mutations?

The number and diversity of mutations in the p53 mutation data base provides indirect evidence that implicates environmental mutagens in human carcinogenesis. The p53 gene has a large mutational target size; more than 280 out of 393 amino acids are found mutated in tumors. We argue that there is possibly a limited involvement of selection for specific mutations in the central domain of the protein, and that the distribution of DNA damage along the p53 gene caused by environmental carcinogens can be correlated with the mutational spectra, i.e., hotspots and types of mutations, of certain cancers. This concept has been validated by experiments with sunlight and the cigarette smoke component benzo[a]pyrene representing the polycyclic aromatic hydrocarbon class of carcinogens. The damage/repair data obtained for these mutagens can predict certain parameters of the mutational spectra including the distribution of hotspots in human nonmelanoma skin cancers and lung cancers from smokers. Future studies with suspected mutagens may help to implicate causative agents involved in other cancers, such as colon and breast cancer, where the exact carcinogen has not yet been identified but an environmental factor is suspected.

Dissolved, particulate and sedimentary naturally derived polycyclic aromatic hydrocarbons in a coastal environment: geochemical significance

Polycyclic aromatic hydrocarbons (PAH) derived from natural precursors have been analysed in superficial sediments and waters in the deltaic area of the Rhône river. This area is characterized by major water and solid inputs from the Rhône river into the Mediterranean Sea. Nine superficial sediment samples were collected in February 1985 and September 1986, and 15 water samples were collected in September 1986, January 1987 and June 1987, with further separation of particulate and dissolved phases. After extraction of lipids, isolation and fractionation of hydrocarbons by HPLC, PAH were analysed by GC and GC-MS. Retene and tetrahydrochrysenes (THCs) were the major naturally derived PAH detected in the Rhône delta. They derive from diterpenoid and triterpenoid precursors, which are common constituents of terrestrial plants. In sediments, intermediate products were absent or at trace levels, suggesting that formation of natural PAH occurred mainly before deposition. Concentrations of retene and THCs were in the range 12.92–52.86 ng g −1 and 16.56–162.68 ng g −1, respectively. Their distributions were different from those of anthropogenic PAH. Despite their common origin, retene and THCs did not show identical distributions and relations to parameters such as total organic carbon and terrestrial n-alkanes; these findings indicate that they follow different transport pathways, as a result of different particle associations. Estimations of retene and THC fluxes and the use of these markers for determining the percentage of ‘terrestrial organic carbon’ are presented. Analysis of water samples confirmed that naturally derived PAH were mainly formed before deposition, in soils of the drainage basin or during the early stages of riverine transport. The distributions of natural and anthropogenic PAH were different, which suggests that the carrier particles of natural PAH were coarser and settled more rapidly than those carrying anthropogenic PAH. However, retene and THCs did not appear to be associated with the same particle types, shown by distributional differences and by the presence of retene in the dissolved phase in contrast in THCs. Consequently, the distributional trends observed in sediments can be explained by the different aquatic transport of the various PAH classes as demonstrated by the analysis of water samples. Instantaneous fluxes were estimated in three seasons for both dissolved and particulate phases. They again showed decoupling between natural and anthropogenic PAH. Fluxes of natural PAH were strongly dependent on the river flow, whereas those of anthropogenic PAH were more dependent on emission rates. The dissolved phase was a significant factor in the transport of retene and of anthropogenic PAH. Naturally derived PAH, and more specifically THCs, appear to be promising tracers of inputs and dispersal of continental organic matter.

Sythesis of methylene-bridged polyarenes

Methylene-bridge polyarenes are a relatively rare class of polycyclic aromatic hydrocarbons whose chemistry is relatively unexplored. Although thet are suspected carcinogenic environmental pollutants, few hydrocarbons of this class are known, and general synthetic approaches are lacking. Convenient syntheses of a series of methylene-bridge polyarenes are now described. These syntheses are based upon the prototype hydrocarbon cyclopenta[def]phenanthrene ( 1) which contains a pre-existing methylene bridge. Polyarenes prepared include 13 H-dibenz[bc,l]aceanthrylene ( 3), 4 H-cyclopenta[pqr]picene ( 5) 4 H-benzo[b]cyclopenta[mno]chrysene ( 6), 13 H-indeno[2,1,7-qra]naphthacene ( 7), and 4 H-cyclopenta[def]dibenz[a,c]anthracence ( 8), of all which were previously unknown. Attempts to prepare 4 H-benzo[c]cyclopenta[mno]chrysene ( 4) by catalytic or chemical dehydrogenation of its hexahydro precursor failed. This is likely due to steric crowding in the fjord region of 4 coupled with resistance to deformation from planarity caused by the methylene bridge. Preliminary findings from mutagenesis assays support the hypothesis that the active mutagenic metabolites of methylene-bridged polyarenes are sulfate esters of alcohol metabolites in the bridge sites.

Relationship between DNA adduct formation and unscheduled DNA synthesis (UDS) in cultured mouse epidermal keratinocytes

Primary cultures of mouse epidermal keratinocytes from SENCAR mice were treated with 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene [B(a)P], (+/-)7 beta-8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+/-)anti-BPDE], and (+/-)7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+/-)syn-BPDE] to examine the relationship between DNA adduct formation and the induction of unscheduled DNA synthesis (UDS). DNA adducts were measured as pmol hydrocarbon bound per mg of DNA, and UDS was quantitated autoradiographically as net grains per nucleus. A good correlation was observed between the levels of UDS detected and the amount of DNA adducts present in the cell population when comparing similar compounds within the linear dose-response range of 0.005 micrograms/ml-0.25 micrograms/ml. A higher rate of UDS for a given level of DNA adducts was interpreted as an increased efficiency of DNA repair. In some cases, an increase in the efficiency of DNA excision repair correlated with lower tumor-initiating activity. For this family of PAH, the concentration below which UDS could no longer be detected was approximately 0.01 microgram/ml. However, DNA adducts were measurable at concentrations of 0.01 and 0.005 micrograms/ml. The limits of detection of the current UDS assay in the SENCAR MEK culture system occurred at hydrocarbon adduct levels of approximately 10 pmol/mg DNA, or approximately 1 adduct per 3 x 10(5) bases. Additionally, the UDS assay was unable to detect DNA repair induced by the weakly carcinogenic PAHs, dibenz(aj)anthracene and 7-methyl-dibenz(aj)anthracene. The UDS assay did detect DNA repair by the more strongly carcinogenic PAH, 6-methylcholanthrene. These results suggest that the present UDS assay with MEKs is a useful assay for the rapid screening of potential genotoxic agents. However, the limits of sensitivity are such that the current assay may be unable to detect a low level of DNA damage induced by some weakly genotoxic (carcinogenic) agents. In addition, while the limits of sensitivity determined in these experiments apply to the polycyclic aromatic hydrocarbon class, other classes of genotoxic compounds such as alkylating agents or crosslinking agents may exhibit different thresholds of detection.

Chromosomal abnormalities in soft coal open-cast mining workers

Chromosome aberration tests on cultured peripheral blood lymphocytes were carried out in two groups of open-cast mining workers engaged in stripping operations (Group I) and digging operations (Group II), in a group of coal cleaning plant workers used as a positive control, and in a group of nonexposed subjects serving as matching controls. Peripheral blood samples in group I and group II miners were collected in March and June of 1984, the antimutagenic potential of long-term prophylactic vitamin administrations (1 g of ascorbic acid given daily for a period of 3 months and 100 mg of vitamin A a day for two 5-day cycles) initiated after the first blood sampling was tested in group II miners. The frequency of aberrant cells (% AB.C.) found in the cultured lymphocytes of group I miners was increased at both times of measurement (2.41 % AB.C. and 2.29 % AB.C.), in group II miners given the vitamin prophylaxis it dropped significantly ( P>0.01) from the initial 3.16 % AB.C. in March to 1.77 % AB.C. in June, and in the group of coal cleaning plant workers (1.30 % AB.C.) it was more or less equal to that of matching controls (1.21 % AB.C.). Implicity, coal dust alone can hardly be made responsible for the rise in % AB.C. It appears that the increase in frequency of chromosome aberrations observed in soft coal open-cast mining workers rather reflects an increased risk of genetic injury due to exposure to ever-present fumes and fire hazards that may give rise to the mutagenic chemicals belonging to a class of polycyclic aromatic hydrocarbons. The antimutagenic effect of ascorbic acid prophylaxis was characterized by a significant drop in % AB.C. and a speed-up of the lymphocyte cell cycle expressed as the proliferating rate index (PRI) whose value rose from the original 1.41 to 1.69, thus reaching the PRI value of matching controls (1.63).

Cytogenetic analysis of peripheral blood lymphocytes in glass workers occupationally exposed to mineral oils

Chromosome aberration tests were carried out in a group of 31 pressed glass makers operating an automatic line of press-and-blow machines known to release mineral oil mists containing relatively high concentrations of the mutagenic chemicals belonging to a class of polycyclic aromatic hydrocarbons (PAH). The workers were exposed to the mineral oil aerosol levels that did not exceed the Czechoslovak maximum allowable concentration limit of 5 mg·m −1 of air. The tests revealed that the frequency of aberrant cells (% AB.C.) and the value of breaks per cell (B/C) ratio found in mineral oil-exposed workers were increased significantly, accounting for 4.65 ± 0.29% AB.C. (0.0532 B/C) vs. 1.13 ± 0.19% AB.C. (0.0113 B/C) seen in matching controls. Also, a higher rate of dicentrics, reciprocal translocations and cells with pulverization was observed in this group of glass workers. These findings are considered as evidence suggesting that these workers might experience an increased risk of genetic injury due to exposure to mineral oil mists.

Effects of a polybrominated biphenyl mixture in the rat and mouse: I. Six-month exposure

A 1973 environmental accident in Michigan resulted in exposure of humans via the food chain to polybrominated biphenyl (PBB). To better characterize the toxicity of the halogenated polycyclic aromatic hydrocarbon class of chemicals, rodents were dosed with PBB and their target organs examined for morphological, histological, biochemical, and selected endocrine changes. Male and female rats and mice were given 125 po doses of PBB over a 6-month period at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg of body weight/day (5 days/week). There was a dose-related decrease in body weight gain in both male and female rats and male mice. Thymus weights were significantly decreased in all rats exposed to 0.3 mg/kg or more of PBB. Dose-related hepatotoxic effects were observed in both rats and mice characterized by marked increase in liver weight with accentuation of hepatic lobular markings. Microscopically, there were moderate to marked swelling, disorganization, and single cell necrosis of hepatocytes, fatty infiltration, bile duct proliferation, and presence of atypical hyperplastic foci. Hepatic porphyrin levels were markedly increased in both rats and mice primarily in females. There was a significant decrease in serum thyroxine (T 4) and triiodothyronine (T 3) suggesting that PBB may interfere with thyroid hormone secretion. There was a significant dose-related increase in serum cholesterol and γ-glutamyl transpeptidase, and a decrease in serum glucose.

Characterization of the effects of known hepatic monooxygenase inducers on male and female rat and mouse kidneys

Few studies have been designed to quantify the response of the mammalian kidney to agents known to induce monooxygenase activity in liver. Therefore, experiments were designed to evaluate the pattern of renal monooxygenase response to three agents representing different classes of inducers: 2,4,2′,4′-tetrachlorobiphenyl (2,4,2′,4′-TCB), representative of the barbiturate class, β-naphthoflavone (BNF), representative of the polycyclic aromatic hydrocarbon class and isosafrole (ISO) as a novel class of inducing agent. Studies were carried out using adult rats and mice of both sexes. Treatment with BNF and ISO stimulated ethoxycoumarin and ethoxyresorufin deethylase activities in renal microsomes from male and female rats and mice, whereas treatment with 2,4,2′,4′-TCB had no effect on either enzyme in rats of either sex. NADPH-cytochrome-c-reductase activity was unaffected by any treatment. In rat renal microsomes, cytochromes P- 450 and b5 were increased by treatment with BNF and ISO but were not altered by 2,4,2′,4′-TCB. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of renal microsomes from male rats treated with BNF showed the appearance of a protein band in the 50– 60000 dalton range which is similar to that observed in liver microsomes following BNF treatment. These studies confirm and extend previous observations that rat kidney is refractory to induction by inducers of the phenobarbital class, but responds to ISO and the polycyclic aromatic class of inducers. In addition, the studies have demonstrated the presence of a protein in renal microsomes after pretreatment of rats with BNF that was not apparent in microsomes from control rat kidneys.

Vehicular exhausts: identification of further carcinogens of the polycyclic aromatic hydrocarbon class.

Vehicular exhausts: identification of further carcinogens of the polycyclic aromatic hydrocarbon class.