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Polycyclic aromatic hydrocarbons are ubiquitous environmental contaminants known to be carcinogenic as well as immunosuppressive. Structure-activity studies have demonstrated that modifications in the number of methyl groups of benzanthracenic compounds lead to major changes in their biological activities such as induction of tumors. In the present study, we investigated the immunosuppressive effects of three benzanthracene derivatives differing by number or position of methyl radicals. 7,12-Dimethylbenz[a]anthracene, 12-methylbenz[a]anthracene, and 7-methylbenz[a]anthracene were tested for their ability to inhibit T-cell proliferation. For this purpose, we employed an in vitro activation model utilizing concanavalin A (ConA) or anti-CD3 monoclonal antibody (anti-CD3 mAb) to induce proliferation of murine T-lymphocytes from B6C3F1 mice. The three compounds inhibited splenocyte proliferation stimulated with anti-CD3 mAb, whereas DMBA and 12-MBA, but not 7-MBA, inhibited ConA-induced lymphoproliferation. Results concerning parameters involving interleukin-2 (IL-2) were correlated with those obtained for lymphoproliferation. IL-2 production and number of IL-2 receptors (IL-2R) per cell were inhibited by the three molecules tested, except for IL-2 production following ConA activation of cells treated with 7-MBA. Only DMBA profoundly affected IL-2 responsiveness, suggesting that this compound may inhibit both G0 to G1 and G1 to S transitions of the cell cycle. Addition of exogenous cytokines such as IL-1 and IL-6 with IL-2, or IL-2 alone, suggested that, for the three compounds tested, IL-1 and IL-6 production are not involved in benz[a]anthracene-induced immunosuppression. These results demonstrate that methylation at both 7 and 12 positions of the benzanthracene ring significantly enhances immunosuppression. In addition, DMBA may act on signal transduction mediated by the T-cell receptor (TCR) and the IL-2R, while this is not the case for 7-MBA and 12-MBA.

Polycyclic aromatic hydrocarbons (PAH) are a common component of soil pollution, yet little is known of the ecotoxicological risks these compounds may pose to life in soil. This article reports the ecotoxicity of five PAHs for two terrestrial isopod species. Isopods were exposed to food contaminated with four different concentrations of either fluorene, phenanthrene, fluoranthene (up to 4 μmol/g), benz[a]anthracene, or benzo[a]pyrene (up to 1.25 μmol/g). Exposure of Porcellio scaber lasted 16 weeks, and no adverse effects on survival, growth, or total protein (only females tested) were observed in any of the treatments. A small but significant reduction in growth of Oniscus asellus was observed at 47 weeks of exposure to 0.125 μmol benz[a]anthraceneṁg−1 dry weight and 1.25 μmol fluoreneṁg−1 dry weight and higher concentrations. A significant stimulation of the reproduction of O. asellus was observed in some of the phenanthrene, fluoranthene, benz[a]anthracene, and benzo[a]pyrene treatments; a larger proportion of the females were gravid, which resulted in a higher number of juveniles per female. Exposure did not significantly affect brood size, weight of the mother after release of the juveniles, or the survival of the juveniles upon starvation. Total protein content of females was significantly reduced at 0.4 μmol fluorene g−1 dry weight and higher concentrations. Growth and protein content of isopods is likely to be affected by PAH exposure only at highly contaminated sites. The ecological consequences of stimulated reproduction and possible DNA damage are poorly understood and require further attention because soil invertebrates may be exposed to PAHs over many generations.

The combination of co-cultivation of hepatocytes and epithelial cell lines with a newly developed perifusion system was used for in vitro studies on drug metabolism and cytotoxicity. This approach improved the viability and enhanced the induction of the biotransforming capacity of the hepatocytes. As demonstrated for the induction of 7-ethoxyresorufin O-deethylase activity by 3-methylcholanthrene or benzanthracene, co-cultured hepatocytes in the perifusion system responded more sensitively to these inducers than without perifusion, most likely owing to stable (steady-state) concentrations of the inducers under the former conditions and rapidly declining concentrations under the latter conditions. The perifusion approach rendered it possible to determine the kinetics of drug metabolism during single or sequential incubations. After induction with 3-methylcholanthrene and phenobarbital, phase I metabolism of lonazolac to the monohydroxylated product in perifused co-cultures closely (87%) approached the values reported for the in vivo production, whereas in stationary co-cultures only 52% could be reached. Likewise, cytotoxic effects could be detected more precisely in the perifused co-cultures. If cells were pretreated with 0.2 mmol/L galactosamine for 3 h, perifusion with increasing concentrations of menadione differentially killed epithelial RL-ET-14 cells and hepatocytes at low and high concentrations, respectively, while in stationary co-cultures no differential effect was observed and only the higher concentrations were cytotoxic for both cells. Prevention by incubation with S-adenosylmethionine of menadione cytotoxicity up to a menadione concentration of 250 micromol/L was seen only in the perifused co-cultures, whereas in stationary cultures only a slight shift of the cytotoxic concentration exerting 50% cell damage to higher values was noted. These results demonstrate the versatile application of perifused co-cultures for studies on drug metabolism including induction of cytochrome P450-dependent enzymes and steady-state kinetics of biotransformation, as well as cytotoxic and protective effects of different drugs.

La methodologie precedemment developpee, par mesure des temps de relaxation du carbone-13, pour decrire la reorientation anisotropique d'une toupie plane asymetrique a ete appliquee aux molecules de benzanthracene et de fluoranthene. Le calcul des coefficients de diffusion rotationnels de ces molecules sous leur forme monomere a necessite la determination prealable de leurs constantes d'auto-association. Les resultats ont confirme ceux deja obtenus dans le cas du chrysene et les temps de relaxation des carbones de l'espece dimere ont pu etre apprehendes.

Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were cultured in vitro. Their capacity to metabolize drugs and xenobiotics was explored with typical cytochrome P450 substrates: ethoxycoumarin (known to be metabolized by several P450s), ethoxyresorufin (essentially dealkylated by P450IA1), and testosterone (specifically hydroxylated at several positions by several P450s). The cells could be kept metabolically active in culture for at least 4 days. Their drug-metabolizing activities were inducible by the usual P450 inducers, like phenobarbital and benzanthracene, but also by Aroclor 1254, a PCB mixture. The results obtained indicate that this experimental model could certainly be very helpful in ecotoxicological studies.

Molecular orbital (MO) evaluations of a series of 14 methyl-substituted benz[a]anthracenes, calculated by the complete neglect of differential overlap ( CNDO 2 ) method, are reported. By quantitative structure-activity relationship (QSAR) analysis, the carcinogenic and mutagenic potencies of these compounds have been shown to be correlated with their electronic structures, namely, with the magnitude of the energy of the lowest unoccupied molecular orbital (LUMO). The log mutagenicity potencies for the series of 14 benz[a]anthracenes are negatively dependent on E(LUMO), with a correlation coefficient of 0.82, which is increased to 0.90 by inclusion in the QSAR of a second variable, namely Q3H, the electronic density in the highest occupied molecular orbital, E(HOMO), of carbon-3. E(LUMO) is also negatively correlated with mouse carcinogenicity of the benzanthracenes, with a correlation coefficient of 0.88 for tumour incidence, and of 0.83 for log carcinogenicity index. The carcinogenicity and mutagenicity of the individual members of this series of polycyclic aromatic hydrocarbons are discussed in terms of the relationships between molecular structure, electron density, metabolic activation and covalent binding of reactive intermediates.

Assessment of the distribution of lymphatic capillaries in the connective tissue underlying tumors is very important when attempting to explain the mechanism by which cervical lymph node metastases arise from tongue cancer. The left lateral border of the hamster tongue was rubbed with a dental cleanser in the control group. In the experimental group, it was further treated with a 2.0% solution of 9, 10-dimethyl 1, 2 -benzanthracene acetone (DMBA) to induce an infiltrated tongue cancer. Frontal sections of the tongue from each group were stained with 5'-nucleotidase (5'-Nase) and the lymphatic capillaries were examined under a light microscope.In the control group, the lymphatic capillaries were present in all connective tissue papillae. These lymphatic capillaries arose from the lymphatic capillary network in the lamina propria mucosae. In the experimental group, the lymphatic capillaries were also present in the connective tissue underlying the tumor so that the connective tissue structure resembled papillae. Lymphatic capillaries underlying the tumor were significantly thicker in diameter than those in the control group. The 5'-Nase activity was lower in the experimental group than in the control group.It is conceivable that an increase in diameter is necessary so that the lymphatic capillaries can absorb a large quantity of tissue fluid. Lymphatic capillaries underlying the tumor always maintained a plexus. This result suggested that the lymphatic capillary network in the connective tissue underlying the tumor was repeatedly built and destroyed as the tumor invaded the muscle layer. An inverse relationship between 5'-Nase activity and the diameter of the lymphatic capillaries was also suggested by the results of this study.Therefore, 5'-Nase staining was very useful for observing the lymphatic capillaries in the connective tissue underlying infiltrated squamous cell carcinoma of the tongue.

The Epstein-Barr virus (EBV) proteins latent membrane proteins 1 and 2 (LMP1 and LMP2) are frequently expressed in EBV-associated lymphoid and epithelial cancers and have complex effects on cell signaling and growth. The effects of these proteins on epithelial cell growth were assessed in vivo using transgenic mice driven by the keratin 14 promoter (K14). The development of papillomas and carcinomas was determined in the tumor initiator and promoter model using dimethyl benzanthracene (DMBA), followed by repeated treatments of 12- O -tetradecanoyl phorbol 13-acetate (TPA). In these assays, LMP1 functioned as a weak tumor promoter and increased papilloma formation. In contrast, mice expressing LMP2A did not induce or promote papilloma formation. Transgenic LMP1 mice had slightly increased development of squamous cell carcinoma; however, the development of carcinoma was significantly increased in the doubly transgenic mice expressing both LMP1 and LMP2A. DMBA treatment induces an activating mutation in the Harvey-ras ( H-ras 61 ) oncogene, and this mutation was identified in most papillomas and carcinomas although several papillomas and carcinomas in K14-LMP1 and K14-LMP1/LMP2A mice lacked the mutation. Analysis of signaling pathways that are known to be activated by LMP1 and/or LMP2 indicated that all genotypes had high levels of activated extracellular signal-regulated kinase (ERK) and Stat3 in carcinomas with significantly higher activation in the doubly transgenic carcinomas. These findings suggest that, in combination, LMP1 and LMP2 contribute to carcinoma progression and that this may reflect the combined effects of the proteins on activation of multiple signaling pathways. This study is the first to characterize the effects of LMP2 on tumor initiation and promotion and to identify an effect of the combined expression of LMP1 and LMP2 on the increase of carcinoma development.

Objective To investigate oral carcinogenesis in hamster induced by the topical application of 7,12-dimethyl benzanthracene (DMBA) to evaluate the different lesions produced and the possible preventive effects of the phenolic compounds apigenin (flavone) and carnosic acid (diterpene). Materials and methods Thirty-two Syrian hamsters were divided into three groups: I: 0.5% DMBA (n = 12); II: 0.5% DMBA + potassium apigenin (n = 8); III: 0.5% DMBA + carnosic acid (n = 12). All the animals were sacrificed after 11 weeks, and a macroscopic and light microscopic study was made of the lesions. Results The largest number of neoplasms, showing the most aggressive biological behavior, corresponded to the control group. The group treated with potassium apigenin ranked second in tumor incidence, although the tumors were not very aggressive behavior. In the group treated with carnosic acid, only one malignancy was recorded, showing the smallest volume of all the recorded tumor lesions. Conclusions Our findings indicate that both potassium apigenin and carnosic acid have chemoprotective effects against carcinogenesis induced by DMBA in hamster.

The functionalized benzanthracenes are useful synthons which can be converted into derivatives such as (V) and (VIII) as well as polycyclic carbazoles like (X).

Binding of polycyclic aromatic hydrocarbons (PAH's) to dissolved humic material (DHM) was examined by using equilibrium dialysis and fluorescence techniques. There was a direct relationship between the hydrophobicity of the PAH and the affinity for binding to DHM. The binding affinity P/sub a/ for benzo(a)pyrene (BaP), benzanthracene, and anthracene decreased slightly as the concentration of DHM increased. The binding of BaP to DHM was completely reversible and the extent of reversibility was unrelated to the sorption time. The rate of binding of BaP to DHM, measured by the quenching to BaP fluorescence, was very rapid and was completed within 5-10 min. The results suggest that the presence of DHM, or other sorptive components of the dissolved organic pool, may affect binding to sediment or suspended particles and thus alter the fate and transport of organic contaminants in aquatic systems.

A computer controlled apparatus for laser flash spectroscopy has been constructed. Nitrogen laser (energy 1 mJ, pulse width 1 ns) is used both for excitation of the sample and for pumping a tunable dye laser which serves as a source of monitoring light. Two different scan modes are possible: (i) a scan with a fixed wavelength of the monitoring light: the temporal evolution of the transient absorption in the range from −2 up to 100 ns can be observed by changing the length of the variable self‐compensating optical delay line, or (ii) a scan with a fixed time delay: the corresponding transient absorption in the range 380–800 nm can be measured. For illustration, the transient absorption spectrum of benzophenone in methylcyclohexane, decay curves of the singlet state of benzanthracene in ethanol in the presence of a quencher, and a ‘‘negative absorption’’ of rhodamine B in nitriles are reported.

A compound I analog is generated from triflato tetrakis (2,6-dichloro- phenyl)porphinatoiron(III) and used to oxidize benzanthracene and pyrene. Benzanthracene is shown to be oxidized primarily via monooxygen transfer from the cpd I complex, while in the case of pyrene, a definitive mechanism was not established, but radical pathways involving dioxygen and water were indicated.

Immune function and hepatic MFO activity were examined in adult and nestling starlings administered a synthetic PAH, 7,12-dimethylbenz[a]anthracene (DMBA). Methods used to examine the starling immune system included immunopa-thology, macrophage phagocytosis, lymphocyte blastogenesis to concanavalin A, and hemagglutination of sheep erythrocytes (SRBC). Concomitant investigations of MFO activity were conducted in starlings exposed to DMBA. Ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-depentylase (PROD) were used as indicators of hepatic MFO activity. Changes in MFO activity were compared to chemically altered immune responses following DMBA exposure. Subcutaneous exposure of adult starlings to 125 mg/kg DMBA resulted in suppression of lymphocyte blastogenesis and antibody production to SRBC. EROD and PROD activity were increased 2.8- and 3.4-fold, respectively. Lymphocyte blastogenesis was impaired in adult starlings orally exposed to 125 mg/kg DMBA. The immune system of nestling starlings exposed orally to 100 mg/kg DMBA was altered, as evidenced by decreased phagocytic ability of macrophages and inhibition of lymphocyte blastogenesis. Oral exposure to DMBA did not induce MFO activity in starlings of either age class. Effects of DMBA on immune function and MFO activity in starlings varied with the age of birds and route and length of chemical exposure.

Saraca asoca (Family Caesalpiniaceae) has been widely used in traditional Indian medicine especially due to its wound-healing property. The present study investigates the chemopreventive property of flavonoids from Saraca asoca (flowers) on 2-stage skin carcinogenesis in mice models. Skin cancer was induced in Swiss albino mice by single topical application of 7,12-dimethyl benzanthracene (100 µg/50 µL of acetone) followed by thrice a week treatment of croton oil for 20 weeks. The topical pretreatment of the flavonoid fraction from S asoca (FF S asoca) was 30 minutes prior to the application of croton oil thrice weekly for 20 weeks. At the end of the experimental period the animals were sacrificed, and the tumor statistics and various marker parameters were studied (enzyme assays, Western blotting). The pretreatment of the FF of S asoca caused significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also, the latency period for the appearance of the first tumor was delayed by S asoca pretreatment. In plant-treated animals there was a significant increase in the levels of reduced glutathione, catalase, and protein in skin when compared with the untreated animals. Conversely, there was a significant decrease in the lipid peroxidation levels. A significant reduction in the expression of ornithine decarboxylase, a key enzyme in the promotion stage of 2-stage skin cancer, in the plant-treated group was also observed. These findings suggest the chemopreventive activity of flavonoids from S asoca on 2-stage skin carcinogenesis.

The spectroscopic properties of an excited singlet electronic state S n ( n ⩾1) of an aromatic compound depend on the type of vibronic coupling of S n with S n −1 . The main spectroscopic criterion for the statistical limit of vibronic coupling is a definite 0,0 transition S 0,0 →S n 0 whose homogeneous lineshape is Lorentzian. This criterion is satisfied by the S 0 →S 3 absorption band of 1,2-benzanthracene. In the excitation spectrum of the S 1 →S 0 fluorescence from isolated 1,2-benzanthracene molecules in a supersonic jet, the origin of the S 0 →S 3 absorption band consists of a single Lorentzian line with a width (fwhm) of 39 cm −1 . Practically the same Lorentzian width is obtained with 1,2-benzanthracene in polymethylmethacrylate by transient spectral hole-burning. The corresponding lifetime of S 3,0 is τ 3,0 =136 fs. The same order of magnitude of τ 3,0 is obtained from the quantum yield of the S 3 →S O fluorescence and the calculated radiative lifetime of S 3 .

The supernatant from human Hep G2 hepatoma cells was examined for typical enzymatic activities involved in the metabolism of xenobiotics. Neither cytochrome P-450 nor b5 was detectable, but associated enzymatic activities were found especially after induction with hydrocortisone (HC) and benzanthracene (BA) suggesting that this Hep G2 supernatant contains cyt P-450 IA1 and IA2. Other critical enzymes are also present, but, as expected, at lower activities than in Aroclor 1254 rat liver S9, except for NADH and NADPH cytochrome c reductase. Results of the Ames test indicate that the induced Hep G2 supernatant is a suitable activator for the evaluation of genotoxicity of indirect mutagens.

An improved method of long-range correlation based on 2D DEPT with suppression of one-bond correlations is demonstrated and evaluated. The experiment has the advantages over other long-range heteronuclear correlation experiments of yielding a pure-phase absorption spectrum with suppression of short-range correlations, and the sequence contains fewer pulses than equivalent experiments previously reported, thereby reducing accumulated errors in pulse duration and phase. The application of the method to assignment is demonstrated with reference to the spectra of the aromatic hydrocarbons fluoranthene, phenanthrene, benzanthracene, and benzo [ g ] chrysene.

The purpose of this study was to explore the use of polycyclic aromatic hydrocarbons (PAH) as organic tracers and to demonstrate how their atmospheric chemical reactivity can be incorporated into a chemical mass balance (CMB) model. PAH signatures were characterized for three combustion sources; residential wood combustion, gasoline spark ignition emissions and diesel engine emissions. The ability to source-differentiate using PAH signatures was tested with a numerical simulation program. Signatures with nine different PAH ranging from benzanthracene to coronene and two smaller groups with four PAH were used. Normalized PAH signatures gave better results than un-normalized signatures. It was possible to distinguish between three sources when a minor source contributed more than 10% of the total. The resulting CMB model was evaluated with ambient data from three different studies for which PAH data existed, and receptor modeling had been undertaken using other tracers. Very reasonable results were obtained. PAH reactivity can strongly influence predicted source contributions under warm daytime conditions.

One year after the Gulf War oil spill, approximately 200 intertidal and subtidal (surface and subsurface) sediments were collected in the areas of Dawhat al Musallamiyah, Dawhat ad Dafi, and Ras Tanaqib along the Saudi Arabian coast as part of the Nearshore Geochemistry Processes Study (Leg II: 16 March–5 April 1992) of the Mt Mitchell Gulf survey. The sediment samples were analysed for total petroleum hydrocarbons and the environmentally important saturated hydrocarbon (SHC) and polycyclic aromatic hydrocarbon (PAH) components of the spilled oil. The target analytes included n-alkanes (C10–C34) and selected isoprenoids, individual and alkyl homologues of the two- through six-ringed PAH compounds and sulphur-containing heterocyclic compounds (38 individual and alkyl-PAHs), and selected cycloalkane biomarkers (steranes and triterpanes). These target analytes were also determined for reference crude oil samples. SHC, PAH alkyl homologue, and triterpane distributions in environmental samples were compared with reference crude oils—Kuwait crude oil, Light Arabian crude oil, and Iranian crude oil—to determine the source(s) and extent of weathering of the spilled oil. Diagnostic hydrocarbon parameters and ratios, especially the plots of the ratios of the C2- and C3-alkyl homologues of the dibenzothiophenes and phenanthrenes/anthracenes (i.e., C2D/C2P vs. C3D/C3P) and the same homologues of the dibenzothiophenes and chrysenes/benzanthracenes (i.e., C2D/C2C vs. C3D/C3C), and the ratio of the source indicator triterpane/trisnorhopanes, TM/TS were useful in differentiating hydrocarbon source(s) and characterizing the weathering of the spilled oil in the samples. From the chemical diagnostic parameters, the Kuwait reference crude oil was determined to be very similar to the Gulf War spilled oil collected during a shoreline survey of oil-impacted beaches of Saudi Arabia in June 1991, shortly after the Gulf War. Asphaltic pavement residual oil found at intertidal sites on Abu Ali and in isolated locations in Dawhat ad Dafi were chemically identified using chemical biomarkers as originating from a source other than oil spilled from the Gulf War. With the SHC and PAH data, a set of chemical characteristics was identified that corresponded to stages of spilled oil weathering. Sediments from exposed habitats generally exhibited an advanced weathering stage; whereas, the moderately exposed and sheltered habitat sediments were typically less weathered at a moderate weathering stage. The advanced stage of weathering was also apparent in the asphaltic pavement sediment. The hydrocarbon characteristics of the subtidal samples were usually dominated by background concentrations of hydrocarbons consisting of both petrogenic PAH and biogenic saturated hydrocarbon signatures.

The cytochromes P-450 detoxicate most chemicals, but activate carcinogens and other toxic chemicals by oxygenating them to reactive intermediates. A new strategy based on the P-450s has resulted in the development of a computer program (COMPACT) and of a programme of enzyme induction studies, as short-term tests to predict the potential toxicity/carcinogenicity of chemicals. Most carcinogens are metabolically activated by P450 I (P-448); P450 IIE and P450 IV also mediate chemical toxicity by producing oxygen radicals. P450 IIB mostly results in detoxication, but where chemicals are oxygenated with difficulty (e.g. phenobarbitone), the cytochrome is induced and futile cycling and oxygen radical formation may result. Oxygen radicals are highly toxic, mutagenic and carcinogenic and mediate much chemical toxicity in small rodents. As P450 genes of man differ from those of rodents, the latter have limited value as surrogates for man in chemical safety evaluation; many short-term tests, such as the Ames test, although valuable in detecting genotoxic chemicals, are similarly limited by their rat liver microsomal activation (S-9) systems. COMPACT is able to overcome both of these limitations, requires no laboratory animals or tissues, and can be conducted from a knowledge of the structure of the chemical, even prior to its synthesis. As the rodent tumorigenicity assay and the Ames test are currently regarded as the standard procedures for safety evaluation, COMPACT was validated against these in a study of 100 miscellaneous chemicals and showed excellent correlations. A quantitative structure-activity relationship (QSAR) for a series of 14 methyl benzanthracenes shows good correlation of mutagenicity with the energy of the lowest empty molecular orbital [E(LEMO)] values of the chemicals. A strategy for COMPACT and P-450 induction studies in chemical safety evaluation is presented.

The Inhibitory Action of 1:2:5:6-Dibenzanthracene on the Growth of the Walker Carcinoma 256 in Rats Maintained on High and Low Protein Diets

The Relation between Growth Inhibition, Toxicity and Protein Metabolism in Rats Treated with 1:2:5:6-Dibenzanthracene

THE œstrogenic action of certain carcinogenic hydrocarbons such as 3 : 4 benzpyrene and 5 : 6 cyclopentane-l : 2 benzanthracene and the carcinogenic effect of œstrogenic hormones (see recent review by Greenstein1) suggested to us a comparison of the cytochemical effects of œstradiol on the vaginal wall of mice with the primary effects of methylcholanthrene on the epidermis studied in detail by Cowdry and his collaborators.

The Absence of a Direct Relation between Growth Inhibition and Sulphur Metabolism After 1:2:5:6-Dibenzanthracene

A non-a-priori method is presented in order to compute from the experiment the apparent rate constant of a diffusion-influenced kinetics reaction with excimer formation in viscous solvents. The case of 1,2-benzanthracene is displayed and an unusual behaviour of the apparent rate constant is obtained, in accordance with a previously described model.

The capabilities of AM1 and MNDO methods for the determination of ground-state geometries and vertical excitation energies of perylene, phenanthrene, 1,2-benzanthracene, and 18 of their planar and nonplanar methyl-substituted derivatives has been investigated. It was found that the MNDO method is not suitable for the sterically strained PAH molecules investigated here. The AM1 calculation of the vertical excitation energies was performed using a CI treatment with 225 singly excited configurations. For the spectral shifts of the S{sub 1} excitation energies induced by methyl substitution, a good correlation between calculated and experimental values was obtained. The deformation-induced spectral shift of the twisted 1-methylperylene was correctly obtained as hypsochromic shift but was calculated too small. The potential energy curves for the twisting motion of the naphthalene moieties in the perylene ground and excited states were evaluated and a vibrational analysis of the low-frequency modes was performed. 44 refs., 7 figs., 3 tabs.

The triplet extinction coefficients eT of acridine, anthracene, benzanthracene, dibenzanthracene, chrysene, pyrene, and pyrene caroxaldehyde were measured at the visible spectral region at maximum triplet‐triplet absorption. We used McClure’s method together with cw lasers as excitation sources to obtain the eT values. Because these triplet extinction coefficients were measured with improved accuracy, we suggest that these compounds be used as standards. We wanted to compare the accuracy of our values with the ones suggested as tentative standards. Further, we tested the validity of McClure’s method on anthracene by increasing the cw laser excitation intensities (power) Iex and recording triplet optical densities ODT. Under the experimental conditions we used, about 100 mW of cw laser power appears to be the upper limit.

There are some indications thtt herpes simplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated in cultured cells infected with HSV. To further investigate the mutagenic activity of HSV type 2 (HSV-2) we used mouse skin as a model system for carcinogenesis. Inoculation of the back skin of 4-week-old Sencar mice with live virus twice per week for one week or with inactivated virus twice per week for two weeks was used to initiate the mouse skin. After initiation with HSV-2, 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied twice weekly for 50 weeks as a promoter. During a period of 52 weeks, no skin carcinoma was found in the experimental groups, whereas 55% of control mice treated with 9, 10-dimethyl-1, 2-benzanthracene (DMBA) and then with TPA-developed skin carcinoma. The results demonstrate that HSV-2 could not substitute for DMBA in this animal model of two-stage skin carcinogenesis.

We report modified neglect of diatomic overlap (MNDO) geometry optimizations and valence-effective Hamiltonian (VEH) band structure calculations on a new ladder-type polymer, poly[2,3–8,9]benzanthracene (PBA). Interest in this new fully fused-ring polymer arises from the fact that its synthesis has been recently achieved. The theoretical results indicate that both the geometric and electronic structures of PBA are to be interpreted as resulting from the interactions between a fully planar polyparaphenylene chain and the ethylenic moieties which bridge it. The VEH calculated bandgap for PBA is high, on the order of 2.86 eV, i.e., a value similar to the one calculated for planar polyparaphenylene itself. This wide bandgap is shown to arise from the [HOMO - 1] and [LUMO + 1] levels of polyparaphenylene, the former (latter) being destabilized (stabilized) by antibonding (bonding) interactions with the ethylenic moieties. Differences between linear and angular annelations are briefly discussed.

A quantitative structure-activity relationship (QSAR) has been derived for the mutagenic activity of 117 aromatic and heteroaromatic nitro compounds acting on Salmonella typhimurium TA100. Relative mutagenic activity is bilin-early dependent on hydrophobicity, with an optimal log P of 5.44, and is linearly dependent on the energy of the lowest unoccupied molecular orbital of the nitro compound. The dependence of mutagenic activity on hydrophobicity and electronic effects is very similar for TA98 and TA100. Mutagenic activity in TA100 does not depend on the size of the aromatic ring system, as its does in TA9. The effect of the choice of assay organism, TA98 versus TA100, on nitroarene QSAR is seen to be similar to the effect previously found for aminoarenes. Lateral verification of QSARs is presented as a tool for establishing the significance of a new QSAR.

Tumors were induced in eastern oysters (Crassostrea virginica) by a mixture of aromatic hydrocarbons, an aromatic amine, polychlorinated biphenyls, chlorinated hydrocarbons, a nitrosoamine and heavy metals. Kidney and enteric tumors developed in oysters following exposure to a mixture containing 3,4-benzopyrene, 1,2-benzanthracene, 2-aminofluorene. N-nitrosodiethylamine, technical chlordane, Aroclors 1242 and 1254, p.p'DDE, cadmium (CdCl2), chromium (K2CrO4) and lead (Pb(NO3)2). The chemical concentrations added to a reference sediment from Long Island Sound were 1 x and 10 x the measured level in sediment from Black Rock Harbor (BRH), Bridgeport. Connecticut (normalized for total organic carbon and acid volatile sulfide content for organic and inorganic compounds, respectively). 2-Aminoflourene and N-nitrosodiethylamine, not measured in BRH sediment, were both added at 0·6 and 6·0 μ/g dry sediment. A 3% prevalence of low-grade renal and gastrointestinal tumors developed after 30 days in oysters fed water-column suspended sediment particulate spiked with the mixture of chemicals. Disease progression was most advanced in enteric adenomas. Both types are comparable to those produced after 30 days in the same organs by chemically contaminated Black Rock Harbor sediment. The action of chemical pollutants reported here represents initial findings in a series of studies designed to test sediment contaminants as causal factors for tumors in oysters.

Organotypic skin models are frequently used for a wide range of applications and latterly also for dermatotoxicological studies. To evaluate their practicability for the investigation of xenobiotic metabolism in human skin we compared three types of organotypic skin models, acquired by purchase from different manufacturers, to a self-constructed in-house model with regard to cytochrome P450 (CYP) isoenzyme expression on mRNA and protein level and the inducibility of these enzymes by aryl hydrocarbon receptor ligands. To induce enzyme activity, models were treated with benzanthracene, liquor carbonis detergens, pix lithanthracis or dimethyl sulfoxide as a solvent control. RNA was isolated by phenol-chloroform extraction and purified. Gene expression patterns were studied by cDNA microarray analysis. Microarray data were confirmed by real-time PCR. For quality control of the models and to detect and localize enzyme expression, immunofluorescence staining was performed with antibodies against CYPs and structure proteins. The immunofluorescence staining demonstrated the regular structure of our models. We could provide evidence for the expression of CYP types 1A1, 1B1, 2E1, 2C and 3A5 in organotypic skin models. The expression of CYP1A1 and CYP1B1 was highly inducible by treatment with liquor carbonis detergens. The proof of the expression and inducibility of CYP enzymes in organotypic skin models suggests that skin equivalents are a valuable tool that can emulate CYP-dependent metabolism of drugs and other xenobiotics in human skin.

A methodology has been developed for measurement of aerobic rates of microbial transformation of polycyclic aromatic hydrocarbons (PAH) in sediment samples. Individual 1 4 C-labeled PAH are added to sediment aliquots in sealed vials containing potassium hydroxide (KOH) traps. Vials containing sterile sediment portions are treated similarly and serve as controls. Sediment microbial activity is halted at intervals by addition of acetone to each vial. Following quantitation of 1 4 CO 2 in each trap by liquid scintillation counting, each sediment portion is extracted with acetone in a micro-Soxhlet apparatus. Extractable 1 4 C is separated into unaltered 1 4 C-PAH and polar transformation products by column or thin-layer chromatography; each fraction is quantified by liquid scintillation or automated thin-layer scanning. Residual 1 4 C is measured by combustion of extracted sediment and liquid scintillation counting of the 1 4 CO 2 evolved. Tests show that the presence of acetone in amounts used in the assay does not significantly alter transformation rates. The measured rate of anthracene transformation was proportional to 1 4 C-anthracene concentration at the substrate level employed, thus suggesting that addition of 1 4 C-labeled substrate does not alter significantly the microbial transformation rate. To date sediments from three locations have been examined: a pristine stream, one receiving runoff from a petroleum storage depot, and a stream receiving a byproduct coking plant effluent discharge. Transformations of 1 4 C-naphthalene, anthracene, and benz(a)anthracene have been observed in the two contaminated streams. Evolution of 1 4 CO 2 as a proportion of substrate added varies greatly between compounds: while 64 percent of 1 4 C-naphthalene transformed during one assay was trapped in KOH, corresponding values for 1 4 C-anthracene and 1 4 C-benz(a)anthracene were 11 and 15 percent, respectively. The principal transformation product in most assays is residual 1 4 C, which presumably has been incorporated into cells in a nonextractable form. Polar extractable metabolites are also quantitatively significant, particularly for 1 4 C-anthracene and 1 4 C-benz(a)anthracene, although thin-layer chromatographic patterns of metabolite formation from 1 4 C-anthracene differ between sediments obtained from waters receiving coking plant effluent and petroleum storage runoff. The assay procedure permits a more valid estimation of microbial transformation rates in sediment than do procedures previously applied.

The fluorescent reporter group, N-(5-FLUORESCEINYL),N′-(3-BORONATOPHENYL)THIOUREA (FABA)has been synthesized. This boronate group makes the reporter specific for cis vic-diols. The reporter group is bound to DNA-adducts formed from the reaction of calf-thymus DNA and benzanthracene trans-10,11-dihydrodiol,8,9-epoxide (anti), benzo(a)anthracene-trans-3,4-dihydrodiol-1,2-epoxide (anti) but is not bound to 3-methylcholanthrene-11,12 dihydro-epoxide. Femtomole quantities of adduct may be detected.

A liquid Chromatographic procedure has been developed to quantify phenalene and its alkyl homologues directly in fuels, utilizing oxidative electrochemical detection to selectively determine these species and the related benzanthracene. The repeatability of the method was better than 5% and the detection limit was found to be 10 mg 1 −1 phenalenes. A number of fuel components which have undergone known refinery processes have been analysed for phenalenes, including catalytically and thermally cracked stocks. No phenalenes were found in straight run fuel components, but high levels were found in fresh cracked components.

Experiments were performed to study the early and late ultrastructural changes during hamster cheek pouch carcinogenesis using a regimen of topical application of 9,10 dimethyl-1-1-2 benzanthracene (DMBA) twice a week in liquid paraffin oil. The DMBA was administered for a period of 2 and 4 1/2 months. Hamsters exposed to DMBA for 2 months developed moderate precancerous changes, whereas the hamsters treated with DMBA for 4 1/2 months developed frank and multiple oral tumors with a cauliflower appearance. The ultrastructural pathological changes seen were considerably increased at 4 1/2 months compared with a 2 month period of DMBA treatment. Untreated and solvent control hamsters cheek pouch treated for 2 and 4 1/2 months with liquid paraffin oil alone did not show any premalignant or malignant changes during this period.

Investigated are temperature dependencies of polycyclic aromatic hydrocarbons (PAH) such as benzpyrene, benzanthracene, benzperylene and others in aerosol which are formed during pyrolisis of naturally occurring and man-made polymers.

Effective diffusivities of polyaromatic solutes in aliphatic solvents were determined from adsorption measurements at ambient conditions with three hydrotreating catalysts of pore diameters 6.2-17.5 nm. Solutes studied were dislike (coronene, 9-phenylcarbazole, tetraphenylporphyrin, and tetra(4-biphenylyl) and rodlike (naphthalene, anthracene, benzanthracene, and dibenz- anthracene) polyaromatics of critical dimensions ranging from 0.74 to 2.18 nm. A modified Wilke-Chang-type correlation was developed to predict bulk diffusivities of the polyaromatic solutes in aliphatic solvents

The presence of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in soils poses a potential threat to human health if exposure levels are too high. Nevertheless, the removal of these contaminants presents a challenge to scientists and engineers. The high hydrophobic nature of PAHs enables their strong sorption onto soil or sediments. Thus, the use of surfactants could favour the release of sorbed hydrophobic organic compounds from contaminated soils. In this work, five surfactants, namely Brij 35, Tergitol NP10, Tween 20, Tween 80 and Tyloxapol, are evaluated on the desorption of PAHs [benzanthracene (BzA), fluoranthene (FLU), and pyrene (PYR), single and in mixture] from a model sample such as kaolin. In all cases, the best results were obtained when Tween 80 was employed. In order to obtain the global decontamination of PAHs, their electrochemical degradation is investigated. It is concluded that the order of increasing degradation for single compounds is BzA > FLU > PYR when they are subject to the same electrochemical treatment. In addition, there is a direct relationship between the ionization potential and the electrochemical degradation of PAH.

Exposure of cells to microsomal enzyme inducers can modify the potency of many carcinogens. We have examined the steady-state level of RNA from the P(1)450 gene and the metabolism of benzo[a]pyrene (BP) in primary cultures of human hepatocytes exposed for up to 4 days to 12.5 microM benzanthracene (BA), and in uninduced control cultures. While the steady-state levels of RNA from the P(1)450 gene were nondetectable in uninduced (DMSO only) human hepatocytes, 12.5 microM BA-induced AHH activity, BP metabolism, and/or P(1)450-specific RNA in hepatocytes from seven human cases were investigated. RNA levels specific for the P(1)450 gene appeared maximal at 24 hr following exposure to BA, whereas, the protein, as determined by AHH enzyme activity from BA-induced hepatocytes, continued to increase up to the last time point examined, 72 hr. BA induction for 96 hr increased metabolism of BP (initial concentration of BP, 10 microM) over a time course of 3, 6, 12, and 24 hr of incubation with BP compared with that of controls. The major metabolites of BP produced by human hepatocytes in culture were the unidentified polar BP metabolite(s), possibly polyhydroxylated. BA induction caused approximately a twofold increase in these metabolites. BA-induced cultures showed an increase in glutathione conjugation compared to that in controls. The percentage of glucuronide and sulfate conjugates remains similar in all cultures. Total binding of tritium label BP to DNA was 1.3-fold to fivefold greater in induced cultures, and related more to total metabolism than to production of a specific metabolite. Exposure of human hepatocytes in vitro to BA leads to a large increase in the steady-state level of the RNA specific for the P(1)450 gene and an increase metabolism of BP.

Acetone extracts of airborne particulates collected at different sites in the greater Copenhagen area were tested for their ability to induce the expression of cytochrome P-450IA1 RNA in a human breast cancer cell line, T47-D. The induction efficiency was expressed as an benz(a) anthracene equivalents, that is, the amount of benz(a)anthracene required to give the same level of induction. A significantly higher level of induction of P-450IA1 RNA was seen with samples collected on days with a smog alert. The inducibility of samples collected in rural areas was lower, but no significant difference in inducibility was found between samples collected in urban and suburban areas. Lack of correlation between the mutagenic activity in the Ames assay and the P-450IA1-inducing activity of the samples suggests that the complex mixture of compounds found in airborne particulates may have different biological activities in the two short-term test systems. Measurements of P-450IA1 inducibility provide a new, sensitive approach to assess the biological activity of material present in air pollution. The presence in airborne particulates of chemical compounds that induce cytochrome P-450IA1 an enzyme responsible for the metabolism of ubiquitous chemical carcinogens, suggests that the general environment may change an individual's response to the impactmore » of exogenous chemicals, including the carcinogens present in cigarette smoke.« less