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PubMedDate not supplied

Localization and characterization of meperidine esterase of rats.

Meperidine esterase of the rat was studied. The enzyme activity was found in the liver microsomes but not in brain tissue or blood. The enzyme had an optimal activity between pH 8.0 to 9.5 and a temperature of 53 degrees-55 degrees C. The heat of activation was found to be 4.6 X 10(6) cal/mol and the KM 1.2 X 10(-4) M. The esterase activity of older male rats (200-350 g) was significantly higher than that of the younger group (150-175 g). There was no significant difference in specific activity of hepatic meperidine esterase between male and female rats, and between rats fasted for 20 hr and phenobarbital- and benzopyrene-treated rats and their respective control groups. However, the liver weight and the microsomal protein yield per g of liver of fasted rats were significantly smaller, and those of phenobarbital- and benzopyrene-treated rats were significantly larger, than those of the control group. The overall enzyme activity per liver of phenobarbital- and of benzopyrene-treated rats was therefore significantly increased. The specific enzyme activities in microsomes prepared by ultracentrifugation and by calcium aggregation were not significantly different, although the ultracentrifugation method resulted in a higher yield of hepatic microsomal protein. The enzyme activities in microsomes prepared by ultracentrifugation/or calcium aggregation and frozen at -20 degrees C up to 22 days were not significantly different from those of freshly prepared microsomes. The enzymatic activity was inhibited by cocaine hydrochloride, isocarboxazid, neostigmine methyl sulfate, alpha-naphthyl acetate, p-nitrophenyl acetate, paraoxon, propoxyphene hydrochloride, phenelzine sulfate, physostigmine sulfate, SKF 525-A, tranylcypromine sulfate, fluoride ions, methanol, and ethanol.

Animals↗
PubMedDate not supplied

Increased cytochrome P-450 activity in Aspergillus fumigatus after xenobiotic exposure.

Microsomal fractions were isolated from Aspergillus fumigatus cultures that had been treated with dimethylsulphoxide (DMSO), ethanol, benzopyrene, phenobarbital or naphthalene. All these xenobiotics increased microsomal cytochrome P-450 content. Cytochrome P-450 reductase activity remained unaffected and no alteration in the microsomal protein profile was detectable by SDS PAGE. Benzopyrene, dimethylaniline, hexobarbitol and p-nitroanisole were metabolised by A. fumigatus microsomes, while aniline, ethoxyresorufin and pentoxyresorufin were not. No xenobiotic elicited a more specific oxidation of any of the substrates. A fumigatus microsomes also catalyzed the cell-free biosynthesis of ergosterol and quantitative analysis of assay metabolites showed that exposure to ethanol, benzopyrene or phenobarbitone in vivo resulted in enhanced ergosterol biosynthesis in vitro.

Aspergillus fumigatus↗
PubMed1975

Identification of polcyclic aromatic hydrocarbons in semi-reinforcing furnance carbon black.

A weighed amount of a "special" semi-reinforcing (SRF) carbon black, made in 1964 and not considered to be typical for furnace blacks, was extracted with triple distilled benzene for 24 hours. The separation of carcinogens from the benzene extract was achieved by gas chromatography on a 5 ft x 0.25 inch stainless steel column packed with 3% OV-1 on chromosorb W. The chromatogram yielded 20 peaks. These peaks were collected, eluted and identified by (a) comparison of retention times, (b) peak enhancement technique, and (c) comparison of their excitation and fluorescence spectra with those of known polycyclic aromatic hydrocarbons (PCAH) standards. The PCAH's identified in SRF-carbon black were: anthracene, phenanthrene, fluoranthene, pyrene, benzo(mno)fluoranthene, chrysene, 1,2-benzanthracene, 9,10-dimethyl-1,2-benzanthracene, 1,2-benzopyrene, 3,4-benzopyrene, perylene, o-phenylene pyrene 1,2-benzoperylene, anthanthrene, and coronene. Of these, 1,1-benzanthracene, 9,10-dimethyl-1,2-benzanthracene, 3,4-benzopyrene and o-phenylene pyrene are known carcinogens. These and others have also been quantitated.

Benzene↗
PubMed1980

Determination of polycyclic aromatic hydrocarbons in fat products by high pressure liquid chromatography.

The method previously described by Gertz [1] for the extraction of 3,4-benzopyrene in meat- and fishproducts has been adapted for butter, margarine, edible oils and fats and extended to other polycyclic aromatic hydrocarbons (PAH): 1,2-benzopyrene, 1,2,3,4-dibenzanthracene, 1,2,5,6-dibenzanthracene and 1,12-benzoperylene. The isolated PAH are determined by high-pressure liquid chromatography on reversed-phase columns with detection by fluorimetry. Recoveries range from 76 to 85%. The detection limit varies between 0.10 and 0.90 ppb. By application of optimized analysis conditions the sensitivity can be increased to 0.01 ppb for each compound.

Benz(a)Anthracenes↗
PubMedDate not supplied

[Air pollution by motor vehicles along the freeways].

Total mass particulates and benzopyrenes have been determined to evaluate the specific pollution by vehicles on a section (6 km) of a highway. The traffic density generated an increase of 30% mass particulates in nighttime and 44% during daylight. Concentrations of benzopyrenes in air have doubled compared to the period before traffic.

Air Pollutants↗
PubMed1975

Drug induction and sex differences of renal glutathione S-transferases in the rat.

Treatment of male rats with 3,4-benzopyrene, 3-methylcholanthrene and phenobarbital resulted in the induction of glutathione S-aryl- and S-aralkyl-transferase activities in kidney cytosol. Benzopyrene produced 77 and 44% increases in aryl and aralkyl activities respectively. Methylcholanthrene caused 73 and 86% increases in the retrospective activities, whereas phenobarbital treatment increased only aralkyl activity (51%). There was no effect on epoxide or alkyl glutathione S-transferase activities with these treatments. Differences were found between the specific activities of the four glutathione S-transferases in females and males, with the following female/male ratios: aryl 0.74; aralkyl 2.37; epoxide 1.52; alkyl 1.33. No changes in Km values were observed relative to drug induction or sex differences. Comparisons are made between the findings of this report and corresponding experiements with liver.

Animals↗
PubMed1976

[Influence of various enzyme inductors and combinations of inductors on DDT residue elimination in rats].

A study was under-taken to investigate the influence of pretreatments with various hepatic microsomal enzyme inducers on the elimination of DDT residues in rats previously contaminated with p,p' -DDT at 5 mg/kg/day, during 20 days. The following inducers were used : phenobarbital (50 a mg/kg/day, i.p.), 3,4-benzopyrene (20 mg/kg/day, s.c.) and norethandrolone (20 mg/kg/day, s.c.), all given during 14 consecutive days. Each inducer was administered singly or in combination with the other two according to a 2 X 2 X 2 factorial experiment. The animals were then sacrificed for the measurement of p,p' -DDT, p,p' -DDD and p,p' -DDE residues in the blood, brain, abdominal fat, liver and kidneys. The results show that phenobarbital lowers markedly the concentration of total residues in the fat tissue and brain and that norethandrolone brings about a reduction of the residues in the blood, brain and kidneys, but not in the fat tissue. On the opposite, 3,4-benzopyrene produces an increase of the residues in the brain, liver and kidneys. Phenobarbital thus appears to be more efficacious than the other two inducers in facilitating the elimination of DDT residues from the fat tissue. In addition, it appears that under the experimental conditions used during this investigation, the elimination of DDT residues is not further accelerated by combining the inducers one with each other.

Abdomen↗
PubMed1986

Immunomodulation by polyaromatic hydrocarbons in mice and murine cells.

Several functionally defined in vitro antibody generating systems were used to assess the immunomodulating mechanisms of the benzopyrenes. When benzo(a)pyrene (BaP) or benzo(e)pyrene (BeP) was incorporated into a T-dependent antibody (TDAb)-producing spleen cell culture system, dose- and time-dependent inhibition of plaque-forming cell responses was observed. Addition of BaP at concentrations as low as 0.002 microgram/ml (7.93 nM) resulted in suppression of the TDAb plaque-forming cell response. BeP-induced suppression was seen at the 2-microgram level (7.93 microM). Time course evaluations demonstrated an early requirement for either chemical in culture in order to induce significant suppression. In vitro incorporation of BaP and BeP into polyclonal antibody-generating cultures also resulted in a dose-related inhibition. Inhibition of these antibody responses was also noted following in vivo exposure of mice to BaP or BeP. Fourteen-day exposure of mice to BaP (40 mg/kg) resulted in 98% suppression of the TDAb response. Polyclonal antibody responses were reduced 50 to 66% following 7 days of chemical exposure. BeP caused 51% suppression of the TDAb response following 14-day exposure of animals. These studies indicate that the suppressive effects of the benzopyrenes are multicellular in origin, occur apart from the carcinogenic effects of the chemicals, and cannot be attributed merely to cellular toxicity.

Animals↗
PubMed1985

[Interaction between cytochrome P-448 and NADP-cytochrome P-450 reductase in reconstituted microsomal membranes].

The regularities of changes in the functional activity of the microsomal monooxygenase system reconstituted by self-assembly from intact rat liver microsomes solubilized with 4% sodium cholate were studied at variable levels of NADPH-cytochrome P-450 reductase and the 3-methylcholanthrene-induced form of cytochrome P-450. Using antibodies against cytochrome P-448, the role of cytochrome P-448 in the overall reaction of benzopyrene hydroxylation induced in the microsomal membrane by a set of molecular forms of cytochrome P-450 was investigated. The effect of NADPH-cytochrome P-450 reductase and cytochrome P-448 incorporation into reconstituted microsomal membranes on benzpyrene metabolism suggests that in intact microsomal membranes benzopyrene metabolism induced by different forms of cytochrome P-450, with the exception of P-448, is limited by reductase is not the limiting component; however, cytochrome P-448 reveals its maximum activity at the cytochrome to reductase optimal molar ratio of 5:1; above this level, the catalytic activity of cytochrome P-448 is lowered.

Animals↗
PubMed1985

Effect of intratracheally instilled benzo(a)pyrene on the pulmonary and hepatic drug-metabolizing enzymes in normal and vitamin A deficient rats.

The effect of intratracheal instillation of different doses of benzo(a)pyrene (0.1, 1.0 and 2.0 mg) on the drug metabolizing enzymes of lung and liver was analysed in rats fed diet with or without vitamin A for 5-6 weeks. Benzo(a)pyrene exposure at 2.0 mg dose only elevated the level of cytochrome P-450 and b5, and activity of benzopyrene hydroxylase in liver, and extent of increase was similar in normal and vitamin A deficient groups. Contrary to this, pulmonary contents of cytochrome P-450 and b5, and benzopyrene hydroxylase activity increased over control values in both the groups even at lower doses of benzo(a)pyrene. Moreover, their values were higher in vitamin A deficient-treated groups compared to normal-treated controls. Increase in these parameters was greater in lung as compared to increase in liver. NADPH cytochrome C-reductase in lung and liver was not affected either by inducing vitamin A deficiency or exposing these rats further to benzo(a)pyrene. Uridine-diphospho-glucuronosyl-transferase (UDP-GT) activity in normal and vitamin A deficient groups was enhanced following exposure to benzo(a)pyrene both in lung and liver. However, activity of this enzyme remained impaired in vitamin A deficient groups, benzo(a)pyrene exposed or not exposed when compared to respective normal controls. Glutathione S-transferase activity remained unchanged following exposure to benzo(a)pyrene both in lung and liver. The apparent increase in hepatic glutathione S-transferase and decrease in pulmonary glutathione S-transferase activity in vitamin A deficiency was only due to vitamin A deficient status of rats with no further effect of benzo(a)pyrene.

Animals↗
PubMedDate not supplied

[The enzymes of mono-oxygenase oxidation in the lymphocytes and liver of persons subjected to chlorophenoxy herbicide exposure].

The activity of benzopyrene hydroxylase (cytochrome P-450IA1) was studied in a mitogen-stimulated culture of peripheral blood lymphocytes from residents of the South Vietnam area treated with chlorophenoxy herbicides in the years of American aggression. The population residing in the untreated territory served as the control. The basal and induced benzopyrene hydroxylase activities, as well as the inducibility ratio were determined for each patient using the "lymphocytic test". The content of antipyrine metabolites and their percentage were estimated in the urine of the same patients using the antipyrine test. The computer processing of data allowed to perform primary analysis of the monooxygenase system in lymphocytes by groups in order to reveal correlations between the content of antipyrine metabolites in the urine and the cytochrome P-450IA1 in blood lymphocytes. The effect of residual amount of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) on the human monooxygenase system is discussed.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2001

Effect of cigarette smoke extract on neonatal porcine vascular smooth muscle cells.

RATIONALE: Cigarette smoke exposure in the perinatal period increases the risk of various prenatal and postnatal complications, including sudden infant death syndrome (SIDS) and persistent pulmonary hypertension of the newborn (PPHN). We investigated the cellular effects of cigarette smoke extract (CSE) in the developing vasculature. METHODS: Vascular smooth muscle cells (VSMC) were isolated from neonatal porcine carotid arteries, splenic arteries, and main and resistance pulmonary arteries. Effects of CSE on VSMC proliferation, viability, apoptosis, and media nitrates and nitrites were evaluated. The effects of known constituents of CSE (nicotine, benzopyrene, acrolein, acetaldehyde), aged CSE, CSE with added hemoglobin, devolatilized CSE, CSE with added dithiothreitol (DTT), and reduced glutathione (GSH) on cell proliferation and viability were assessed. RESULTS: CSE caused a dose- and time-dependent decrease in neonatal VSMC numbers isolated from all four sites, mainly as a result of increased cell necrosis and not apoptosis. Nitrates and nitrites were below the threshold of detection. Nicotine and benzopyrene did not affect cell counts, while acrolein and acetaldehyde decreased cell counts in a dose-dependent manner. Addition of hemoglobin, devolatilization, and the addition of DTT or GSH slightly decreased CSE inhibition. CONCLUSIONS: CSE causes necrosis of neonatal VSMC, and this toxicity is mediated mainly by volatile components such as acrolein and acetaldehyde, possibly in association with nitric oxide and carbon monoxide.

Acetaldehyde↗
PubMed1984

Induction by 9-hydroxyellipticine of aryl hydrocarbon hydroxylase in perinatal rat liver and in primary fetal hepatocytes in culture.

In neonatal and, to a lesser extent, in fetal rat liver, 9-hydroxyellipticine was able to promote the induction of cytochrome P-450, supporting especially aryl hydrocarbon hydroxylase (AHH) but not aldrin epoxidase activity. The examination of benzopyrene metabolites by high performance liquid chromatography (HPLC) or by benzopyrene-DNA adducts formation shown that, as in adult animals, the formation of hydroxylated metabolites in position 9,10 was enhanced. In primary fetal liver cells culture, similar effects were observed. Furthermore, the presence of glucocorticoids in the culture medium was not required for the induction of AHH by 9-hydroxyellipticine (9-OHE).

Alkaloids↗
PubMed1988

Chromosome aberrations in cultured central mudminnow heart cells and Chinese hamster ovary cells exposed to polycyclic aromatic hydrocarbons and sediment extracts.

1. Genotoxicity experiments were conducted with cultured fish cells to determine if the high frequency of epidermal papillomas observed in lemon sole from Sturgeon Bank, where a sewage treatment plant discharges, could be correlated with contamination of the sediments with chemicals such as 3,4-benzopyrene. 2. The frequency of chromosome aberrations was measured in cultured Umbra limi heart (U1-H) and Chinese hamster ovary (CHO) cells following exposure to the polycyclic aromatic hydrocarbons (PAH) 3,4-benzopyrene (BP), 1,2,5,6-dibenzanthracene (DBA), 1,2-benzanthracene (BA), and pyrene (PY), activated using S9 prepared from rainbow trout liver. 3. An increase in the chromosome aberration frequency was only observed following exposure to fish S9-activated BP in both cell lines. 4. Following exposure of the cells to both Sturgeon Bank and Spanish Bank sediment extracts, it was determined that a higher level of toxic and genotoxic activity was associated with the Sturgeon Bank sediments. 5. Since the detection of PAH genotoxicity requires the presence of S9, and since a higher level of genotoxic activity was noted following sediment extract exposures with no S9 present, this suggests that the extracts contain a complex mix of chemicals, some of which express genotoxic activity. 6. An assessment using the micronucleus test failed to indicate in vivo genotoxicity in fish collected from Sturgeon and Spanish Banks. 7. It was, therefore, difficult to associate the observed sediment genotoxicity with the previously noted high incidence of epidermal papillomas in lemon sole from this area.

Animals↗
PubMed1992

Selenium in the treatment of heavy metal poisoning and chemical carcinogenesis.

Selenium (Se) has been shown to counteract the toxicity of heavy metals such as cadmium, inorganic mercury, methylmercury, thallium and to a limited extent silver. Although not as effective as Se, vitamin E significantly alters methylmercury toxicity and is more effective than Se against silver toxicity. Vitamin E is very effective against lead toxicity but Se has little effect. The presumed protective effect of Se against cadmium and mercury toxicity is through the diversion in their binding from low molecular weight proteins to higher molecular weight ones. Se appears effective in counteracting the chemical carcinogens (3-methyl-4-dimethyl-aminoazobenzene, 2-acetylaminofluorene, diethylnitrosamine, aflatoxin, 7,12-dimethylben (a) anthracene, benzopyrene and 3-methylcholanthrene) used to induce skin, liver and mammary tumors, but much less effective against those (dimethylhydrazine, azoxymethane, methylazoxymethanol, bis (2-oxopropyl) nitrosamine, benzopyrene, 1 methyl-1-nitrosourea and n-methyl-n-nitro-nitrosoguanidine) used to produce tumors in the colon, lungs, trachea and pancreas in laboratory animals. In contrast, Se many even increase pancreatic carcinomas in animals treated with bis (2-oxopropyl) nitrosamine. The health implications in humans of Se and heavy metal toxicities and in cancer are discussed.

Animals↗
PubMed2005

[The influence of occupational exposure and smoking on lung ventilation of coke oven workers].

OBJECTIVE: To study the influence of occupational exposure and smoking on lung ventilation function of coke oven workers. METHODS: Environmental monitoring was performed on the top, side and bottom of some coke ovens. Lung ventilation function test was performed in 234 coke oven workers. RESULTS: The poison concentration in environment had such tendency as it was the highest on the top, then the side, and the lowest at the bottom. The standardized forced expiratory volume in the 1st second (FEV(1), 90.8% +/- 8.6%) and forced expiratory rate (FEV(1)%, 95.4% +/- 12.4%) of those coke oven workers who smoked were significantly lower than those non-smoking workers (100.9% +/- 14.3%, 108.9% +/- 17.6%); among those smoking workers, the partial correlation coefficients between forced vital capacity (FVC) and benzene soluble, benzopyrene, and smoking index were -0.249, -0.187 and -0.368 respectively; and the coefficients between FEV(1) and the three aspects were -0.255, -0.191 and -0.388; and the coefficients between FEV(1)% and them were -0.131, -0.107 and -0.065. Among those non-smoking workers, the coefficients between benzene solubles and FVC, FEV(1) and FEV(1)% were -0.154, -0.052 and -0.176, and between benzopyrene and them were -0.121, -0.037 and -0.159. CONCLUSION: The lung ventilation function of coke oven workers has certain negative correlation with both occupational exposure and smoking.

Adult↗
PubMed2006

Anticarcinogenic and antiplatelet effects of carvacrol.

AIM: To investigate the effect of carvacrol on chemical carcinogenesis, cancer cell proliferation and platelet aggregation, and to find possible correlation between all these processes and the antioxidant properties of carvacrol. MATERIALS AND METHODS: 3,4-benzopyrene-induced carcinogenesis model using Wistar rats was used. Leiomyosarcoma cells from Wistar rats were used to study carvacrol antiproliferative activity in vitro. The carvacrol antiplatelet properties were investigated with platelet aggregation assay and flow cytometry technique. The production of thromboxane B2, final metabolite of platelet aggregation, was evaluated by radioimmunoassay. RESULTS: Our study revealed significant anticarcinogenic properties of carvacrol. We observed 30% decrease of 3,4 benzopyrene carcinogenic activity in vivo. Antiproliferative activity of carvacrol (IC(50)) was 90 microM and 67 microM for 24 h and 48 h of incubation of cells, respectively. Carvacrol possessed also mild antiplatelet effect, inducing the decrease of thromboxane A2 production in platelets and as a result - restrictive expression of the GPIIb/IIIa platelet receptor. CONCLUSION: Our data demonstrated that carvacrol possesses anticarcinogenic, antiproliferative and antiplatelet properties.

Animals↗
PubMed1982

Evaluation of the cancerogenic risk in oil tankers during refitting.

Polycyclic aromatic hydrocarbons (PAH) concentrations were measured in particles collected in oil tankers during refitting operations in which oxyacetylene flames were used. High levels of benzopyrene (8.3 +/- 7.2 mg/1000 m3) and nitrogen oxides (from 2 to 20 ppm) were detected. The fraction of collected smoke, soluble in cycloesane, was injected into the peritoneum of Balb/C mice. The frequency of sister chromatid exchange (SCE) induced in bone marrow cells was evaluated. A significant and dose-related increase of SCE was seen, which was comparable to that induced by pure PAH. Based on these results, the presence of other mutagenic substances in addition to benzopyrene was suspected. Chemical and biochemical results confirmed epidemiological evidence of an increased risk of lung and bladder cancer in workers operating inside oil tankers. The authors propose the use of this coordinated approach for an effective primary cancer prevention program in the work place.

Air Pollutants↗