Besemer, A.C.; Kanij, J.
The leachability of polycyclic aromatic hydrocarbons from coal ash into aqueous systems was studied. Carbon-14-labeled 3,4-Benzopyrene (BaP) was deposited on coal fly ash by adsorption from the liquid phase in quantities of about 10 ??g/g ash. After a thermal treatment in air at 120??C for 2 hours
Pylev, L N; Roe, F J.C.; Warwick, G P
Injection and recovery experiments of tritiated 3,4-benzopyrene (BaP) injected alone or with particulate carriers into hamsters were performed. After 21 days, asbestos or carbon black carriers had significantly increased the retention of BaP in the lung. Elimination was rapid at first (2 weeks: and little influenced by carrier; slower rate of elimination was noted after that. Carriers increased recoverable macrophages but decreased the amount of radioactivity per macrophage. Radioactivity was similar in all groups for kidney, liver, blood, feces, and urine.
Full Text Available This paper reports a screening results of the secondary metabolites composed in Spathodea campanulata Beauv stem bark, evaluate inhibiting activity of malondialdehyde (MDA on rat’s cancer model exposed with benzopyrene, and the histology of its lung. The secondary metabolite of the stem bark fraction consisted of alkaloids, flavonoids-phenolic, terpenoid and steroid compounds. The isolated fraction contained of these metabolites significantly indicate bioactivity by reducting of malondialdehyde (MDA level, and also histology appearance of the lung tissue prepared from the benzopyrene-exposed rat indicated a curative activity.
Bories, G; Tulliez, J; Peltier, J C; Fleckinger, R
After an oil spill, a coastal zone was polluted and wild mussels were contaminated by paraffinic and naphtenic hydrocarbons and 3,4-benzopyrene. The evolution of this contamination was followed. Normal levels were re-established after a month and a half. Normal paraffins were metabolized faster than other hydrocarbons.
Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.
Relation between atmospheric pollution in urban and rural localities and mortality from cancer, bronchitis, and pneumonia, with particular reference to 3:4-benzopyrene, beryllium, molybdenum, vanadium, and arsenic
Lung cancer mortality was strongly correlated with smoke density in 26 areas of northern England and Wales, in 45 districts of Lancashire and the West Riding of Yorkshire, and in 30 county boroughs (smaller correlations within London). Social conditions partially explain the correlations. Males with bronchitis and pneumonia and females with bronchitis show similar correlations with smoke. Cancers of stomach and intestine show correlations in county boroughs. Statistical eliminative process shows 3:4-benzopyrene (BP) to be the hydrocarbon of prime importance in lung cancer and bronchitis, with 1:12 benzoperylene contributing. BP was not related to penumonia. Other cancers of males, but not those of females, correlated with hydrocarbons. Spectrographic analyses and statistical elimination of 13 trace elements show Be and Mo to be strongly associated with lung cancer; As, Zn, and V are also weakly correlated. In bronchitis Mo is important for both sexes; Be, As, and V are also important for males.
Sadikovic, Bekim; Rodenhiser, David I.
Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-α. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer
Waibel, M; Wanner, H U
Measurements of particulate matter and 3,4 benzoyrene were carried out at six measuring points in and around Zurich in 1971/72. The measuring points differed according to their immediate surroundings; they were subdivided into industrial zone, heavy traffic spots, residential area, and recreation ground. The correlations were calculated to clarify the connections between emissions and meteorological influences including temperature, inversions, humidity, air pressure, wind strength, visibility, and sunlight. The annual average values for the aerosol concentration were highest (160-181 microgram/cu m) where traffic is very heavy. An industrial center and a residential area of the old part of the city assumed a middle position. The modern residential section of Triemli measured the lowest concentration, 100 micrograms/cu m. The annual average concentrations for BaP were 5.3 ng/cu m for the industrial center, 5.5 and 7/7 ng/cu m for Paradeplatz and Albisriederplatz and 4.1 ng/cu m for Triemli. A high BaP concentration of 6.4 ng/cu m was measured in the old residential section. A correlation between the aerosol concentration of the air and the mortality from stomach cancer was found. Particularly pronounced was the influence of air pollution on mortality due to respiratory diseases. It tripled from the zone with lowest aerosol concentration (less than 80 micrograms/cu m) to the zone with highest air pollution (more than 135 micrograms/cu m). Compared to West German and U.S. cities the aerosol and BaP concentrations measured in Zurich were rather high.
Santos, F.L.; Cunanan, S.A.
An analytical methodology developed for trace amounts of polychlorinated biphenyls (PCB's) in water was described. The water sample was extracted with hexane and the extract passes through a florisil column. The cleaned extract was concentrated and then analyzed by gas chromatography using an electron capture detector. The methodology has an efficiency of 85% recovery for PCB spiked at a concentration level of 1 ppm. Minimum detection limit obtained was 0.5 ppm PCB in water. A total of 27 water samples were collected and analyzed during the period January - June 1978. No PCB's were detected in the samples. (author)
Effects of chemical carcinogens of hemopoiesis, immunopoiesis and viral oncogenesis. Technical progress report, December 1, 1977--September 30, 1978. [Mechanisms of potentiation of viral leukemogenesis by MMS, benzopyrene, and DMBA
OKunewick, J.P.; Raikow, R.B.; Meredith, R.F.
During the past year we have concentrated on defining the circumstances under which methyl methanesulfonate (MMS), benzo(a) pyrene (BP), and 7,12-dimethylbenz(a)anthracene (DMBA) interact with Friend virus (FLV) to produce leukemia. The optimum scheduling for each and also the effective dose levels of the chemicals have been partially determined. There are at least three critical factors which govern whether or not a leukemogenic interaction can be shown between the chemical agents and the virus. These are chemical dose, virus dose, and their relative time of administration. The most critical of these is virus dose. The optimum virus dose is that which results in between 25 and 40% incidence of leukemia within 40 days after virus infection when virus is given alone. The chemical carcinogens have a lower dose threshold, below which no significant potentiating effect can be observed. The only upper limit would appear to be acute drug toxicity. The third element, timing, is equally critical and varies according to the chemical. This variation may reflect different mechanisms of action by the chemical agents and/or different pharmacology. Data on the effects of MMS, BP, and DMBA on the immune system have indicated that the viral enhancement is probably not dependent on this function. Further enhancement of the potentiation of viral leukemogenesis was observed using benzo(a)pyrene and caffeine, indicating that the inhibition by caffeine of DNA repair may be an important factor in virus potentiation. (ERB)
Ibraev, N.Kh.; Zhunusbekov, A.M.
Temperature influence on triplet-triplet (T-T) energy transfer between molecules of eosin and 3,4-benzopyrene is studied. Polyvenylbuteryl films have been used in capacity of polymer matrix. Calculation has being carried out on spectral-kinetic unit. It is revealed, that 3,4-benzopyrene triplets have been formed in polymer matrix after end of T-T energy transfer. These triplets join in a reaction of mixed triplet-triplet annihilation with non-blow out triplets of eosin and its sensitize slowed fluorescence (SF) of donor. This explains non-exponent character of eosin's dumping kinetics. Non-linear dependence of SF output ration to eosin phosphorescence output under presence of 3,4-benzopyrene molecules in film indicates on process of mixed annihilation. Fractal character of SF donor and acceptor has been evidenced about microscopical distribution of phosphor in polymer. 13 refs., 5 figs
The remo val of hazardous organic pollutants such as polychlorinated biphenyls (PCB's), polycyclic aromatic hydrocarbons (benzopyrene, dibenzoanthracene), pesticides (DDT, lindane), and pharmaceutical products ( diclofenac, ibuprofen, carbamazepine) from waste water is a growing concem in environmental science and technology. Therefore, innovative methods for water remediation in removing contaminants from waste sites need to be examined. This work explores the use of Pulsed Corona Disc...
206 workers of three pitch coking plants, who had been exposed for an average of 4 years to fumes containing 3,4 benzopyrene, were examined. No occupational carcinoma or precancerous foci were detected. The only statistically significant findings were chronic atrophic inflammations of upper respiratory pathways (26%). This investigation is the initial stage in a long-term study of this group of workers. A plan for preventive examinations (including specialized ones), contraindications applicable for this type of job, methods for epidemiological investigations and the follow-up of workers after leaving this work, are described in detail.
Seliger, H H
The directions of the research program in understanding the dynamics of the natural phytoplankton populations of the Chesapeake Bay, the methodology, the statistical analysis, and the description of the system are parallel to the requirements for environmental impact studies. Results are reported for the following studies: development of instrumentation and the synoptic isopleth methodology for relating the dynamic distributions of natural phytoplankton populations to water circulation patterns; phytoplankton cage experiments for assessment of nutrient dynamics; sub-lethal concentrations and effects of polycyclic aromatic hydrocarbons; and studies on concentration and time kinetics of induction of liver aryl hydrocarbon hydroxylase system in Fundulus heteroclitus by benzopyrene and 3-methyl cholanthrene. (HLW)
Stocks, P; Campbell, J M
This report discusses a two-year comparison of deaths from lung cancer with environmental histories, including smoking and pollution character of residence, of British men aged 45 to 74. In rural areas, lung cancer increases almost linearly with smoking, the increment being 1 death per 1000 for each 13 cigarettes. Pipe smoking is about 1/3 as hazardous as cigarette-smoking. In mixed rural-urban areas, rates in light and moderate smokers were higher than rural but not so with pipe or heavy smokers. There was a higher death rate in every group in urban area, but rate of mortality increase with increasing cigarette exposure was greater for those living in rural areas. Urban/rural ratio was about 9 for nonsmokers decreasing to almost 1 for heavy smokers. Smoking contributes 1/2 of lung cancer in urban area; urban factor contributes 3/8 (absolute excess in every group). Benzopyrene concentration of urban area was 8 to 11 times that of rural areas and gradient corresponds to urban/rural ratio for nonsmokers. Benzopyrene/death correlation was good if assumed combined intake is considered.
Sanitary impact of cleaning operations following the pollution bred by the Erika wreck: evaluation and prevention. Synthesis of available data and recommendations; Impact sanitaire des operations de nettoyage consecutives a la pollution engendree par le naufrage de l'Erika: evaluation et prevention. Synthese des donnees disponibles et recommandations
The I.N.E.R.I.S. (Institut National de l'Environnement Industriel et des Risques) report relative to the consequences of cleaning operations following the pollution bred by the Erika wreck gives the following conclusions: whatever the pollutants are, the carcinogen risks by pulmonary way are negligible for people assigned to the beaches cleaning; the general carcinogen effects, linked to benzopyrene in organism after skin crossing, have been evaluated as negligible; there is a non negligible risk for the embryo-fetal development linked to the benzopyrene skin crossing; It is not possible to tell if the skin cancer risk is or not negligible, because of the uncertainty of the dose effectively absorbed by the skin and the lack of acceptable toxicological references; the risks linked to the volatile organic compounds are negligible; an uncertainty exists on the risks linked to the thiophene family that have not been determined, because of the deficiency of base data. For the second study, whatever the studied scenario, the R.I.V.M. (Riijksinstituut Voor Volksgezondheid en mileuhygiene) Dutch organism report concludes to a risk qualified as acceptable for the voluntary workers and professionals, included the birds cleaners. The risk of skin cancer consecutive to the skin exposure has been characterized with a dose response relationship model coming from previous works of the R.I.V.M. (N.C.)
Full Text Available This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH- induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1 for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs.
Full Text Available The aim was to explore the eventual role of bacteria in the induction of lung cancer by smoking habits. Viable bacteria closely related to the genus Bacillus were detected at high frequencies in lung-cancer biopsies. Similar, if not identical, microbes were isolated from cigarettes and in smog. Bacteria present in cigarettes could be transferred to a physiological solution via a smoker device that mimicked their potential transfer during smoking those bacteria produce exotoxins able to open transmembrane pores. These channels can be used as a way to penetrate cells of benzopyrenes and other toxic substances present in tobacco products. We hypothesize that Bacillaceae present in tobacco play a key role in the development of lung cancer.
Ibraev, N.Kh.; Latonin, V.A.; Satybaldina, D.Zh.
The paper is devoted to study of decay mechanism of phosphors molecules triplet states in the Langmuir-Blogett (L-B) films. The L-B-films have being prepared on the base of anthracene, pyrene, 3,4-benzopyrene and 1,2-benzanthracene molecules. Spectral and kinetic investigations were carried out in photons counting regime. Long-lived luminescence was observed under excitation of the LB-film by nitrogen laser radiation (λ=337 nm) .Spectrum of the long-lived luminescence coincides with spectrum of fast fluorescence of same film. Received spectral data indicate on similarity of LB-films structure of aromatic molecules and its crystals. It was defined, that deactivation of triplet states of aromatic molecules in LB-films has being carried out mainly in the result of annihilation of triplet excitation. 14 refs., 2 tabs., 5 figs
Epstein, S S
Exposure of Paramecium caudatum to suspensions of 3,4-benzopyrene, followed by long wave ultraviolet irradiation, results in cell death at times related, inter alia, to carcinogen concentration. Prior to death, the cells exhibit progressive immobilization and blebbing. This photodynamic response is a sensitized photo-oxidation, as it is oxygen-dependent and inhibited by anti-oxidants, such as butylated hydroxy anisole and ..cap alpha..-tocopherol. Protection is also afforded by other agents, including Tweens, tryptophan and certain fractions of plasma proteins. No evidence was found for the involvement of peroxides or sulfhydryl groups. The correlations between photodynamic toxicity and carcinogenicity in a large series of polycyclic hydrocarbons is under investigation. Assays of air extracts for photodynamic toxicity are in progress. Significant toxicity has been found in oxygenated besides aromatic fractions.
Vo-Dinh, Tuan; Scaffidi, Jonathan; Gregas, Molly; Zhang, Yan; Seewaldt, Victoria
Fiber-optic nanosensors are fabricated by heating and pulling optical fibers to yield sub-micron diameter tips and have been used for in vitro analysis of individual living mammalian cells. Immobilization of bioreceptors (e.g., antibodies, peptides, DNA) selective to targeting analyte molecules of interest provides molecular specificity. Excitation light can be launched into the fiber, and the resulting evanescent field at the tip of the nanofiber can be used to excite target molecules bound to the bioreceptor molecules. The fluorescence or surface-enhanced Raman scattering produced by the analyte molecules is detected using an ultra-sensitive photodetector. This article provides an overview of the development and application of fiber-optic nanosensors for drug discovery. The nanosensors provide minimally invasive tools to probe subcellular compartments inside single living cells for health effect studies (e.g., detection of benzopyrene adducts) and medical applications (e.g., monitoring of apoptosis in cells treated with anticancer drugs).
This document provided an overview of ambient air pollutant trends in Alberta. The report discussed the following pollutants having effect on human and environmental health: carbon monoxide (CO), hydrogen sulphide (H2 S ), nitrogen dioxide (NO 2 ), sulphur dioxide (SO 2 ), ozone (O 3 ), fine particulate matter (PM 2 .5), benzene, and benzopyrene. Each of these pollutants was described. The report provided data on annual average concentration trends and annual 99th percentile concentration as an indicator of peak concentrations. A map illustrating air quality monitoring stations in 2006 was also provided. The findings revealed that mean annual CO levels were the lowest they have been since 1990; hydrogen sulphide concentrations have fluctuated in time since 1990; most Edmonton and Calgary area stations showed significant decreasing trends in annual average NO 2 levels since 1990; and higher SO 2 concentrations have been found in the industrial areas of Alberta, such as the Redwater and Scotford oil sands locations. tabs., figs
Hagstroem, U.; Zoukatas, N.; Kutscher, E.; Megas, L.
The three main principles of combustion, namely burning over the fuel bed, under the bed, and the inverted flame have been investigated. Combustion under the fuel bed rendered the lowest emission of carbon monoxide, hydrocarbons, benzopyrene, particulates and tar. Emission is also reduced by preheating the primary incoming air. Burning of pine gives variable emissions whereas birch tree and lying log gives satisfactory combustion. High flame intensity and Reynolds number of the flame zone in the interval 5 to 8 x 10/sup 3/ also give low emission. A conventional wood burner with its flame over the fuel bed and with a water cooled combustion chamber produces 100 times more carbon monoxide than an advanced construction.
Bleijenberg, A.N.; Davidson, M.D.
There is no market price for environmental pollution, simply because of the fact that there is not a market for the environment. However, it is possible to calculate so-called shadow prices for environmental pollution. The calculation method can be summarized as follows: determine the price that exist when there would be a market for the environment. In many cases the calculation must be based on environmental targets as determined by the government. Based on that method and on available data and information, shadow prices are estimated for 18 different pollutants: CO2, CO, CH4, SO2, NH3, NOx, volatile organic materials, final wastes, phosphates, nitrates, COD, fine dust, toluene, benzene, benzopyrene (to air and water), zinc (to water), and copper (to water). 7 figs., 5 tabs., 43 refs
Hamzah M. Maswadeh
Full Text Available Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS. Anticancer drug etoposide (ETP was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes. The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.
Schrimpff, E.; Klemm, O.; Eiden, R.; Frevert, T.; Herrmann, R.
A simple device for sampling fog water is described (modified passive Grunow sampler), and analytical results as were found in rain and fog waters are reported. All samples were taken in the northern part of the Frankenwald mountains (near Bad Steben) from November 1982 until March 1983. Specific conductivity (..mu..Sxcm/sup -1/, 20/sup 0/C), titration acidity, Cl/sup -/, NO/sub 3//sup -/, SO/sub 4//sup 2 -/, total hardness, Ca, Na, Fe, Cd, Pb, TDOC and the polycyclic aromates fluoranthene and 3.4-benzopyrene were continuously higher in fog than in rain water. pH's were remarkably decreased in fog water. Here extreme results were measured in the first two weeks of March with pH 2.5, and acidities proportional2 mequivxl/sup -1/. Possible reasons for such extraordinary concentrations are discussed meteorologically as well as hydrochemically.
Sadikovic, Bekim; Haines, Thomas R; Butcher, Darci T; Rodenhiser, David I
Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and oncogene activation. Potential links exist between environmental agents and DNA methylation, but the destabilizing effects of environmental exposures on the DNA methylation machinery are not understood within the context of breast cancer aetiology. We assessed genome-wide changes in methylation patterns using a unique methylation profiling technique called amplification of intermethylated sites (AIMS). This method generates easily readable fingerprints that represent the investigated cell line's methylation profile, based on the differential cleavage of DNA with methylation-specific isoschisomeric restriction endonucleases. We validated this approach by demonstrating both unique and reoccurring sites of genomic hypomethylation in four breast carcinoma cell lines treated with the cytosine analogue 5-azacytidine. Comparison of treated with control samples revealed individual bands that exhibited methylation changes, and these bands were excized and cloned, and the precise genomic location individually identified. In most cases, these regions of hypomethylation coincided with susceptible target regions previously associated with chromosome breakage, rearrangement and gene amplification. Similarly, we observed that acute benzopyrene exposure is associated with altered methylation patterns in these cell lines. These results reinforce the link between environmental exposures, DNA methylation and breast cancer, and support a role for AIMS as a rapid, affordable screening method to identify environmentally induced DNA methylation changes that occur in tumourigenesis
Geacintov, N.E.; Pope, M.
This project is concerned with studies of biological activity-structure relationships in which the mechanisms of interaction of ionizing radiation and benzopyrene (PB) compounds with DNA are being investigated and compared. Emphasis is focused on effects of DNA conformation on its mechanisms of interaction with ionizing radiation, on the influence of structure and stereochemistry of BP metabolites on mechanisms of DNA damage, and on influence of DNA conformation on interactions between BP metabolites and DNA molecules, and the structures of the complexes and adducts which are formed. One basic theme of this project is the use of photoexcited states of BP and nucleic acids as probes of these interactions. In part I of this report, recent progress on elucidating the structures of selected BP-oligonucleotide model adducts by high resolution NMR and gel electrophoresis techniques is summarized. It is shown that the stereochemical properties of benzo[a]pyrene diol epoxide-DNA adducts play a crucial role in determining their interactions with certain exonucleases. These results provide useful models for deriving a better understanding of differences biological activities of BP compounds and the relationships between mutagenicities and the structure properties of BP-DNA adducts. In Part II of this report, a new time-resolved method based on picosecond laser pulse techniques for elucidating the electronic levels involved in electron photoemission and electron transfer in BP and nucleic acid solids is described
Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.
Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 microgram benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi, Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.
Meiss, R.; Heinrich, U.; Offermann, M.; Themann, H.
Female NMRI mice aged 9-12 weeks were each given a single subcutaneous injection of 0.5 ml of a suspension containing either the total extracts or the polycyclic aromatic hydrocarbon (PAH) fraction of airborne particles. Both the total extracts and PAH fractions contain 3 ..mu..g benzopyrene. After about 15 months the livers were removed from the animals, which had by that time developed tumors at the injection site, and were subjected to electron-microscopical study. The essential alterations were observed in the nucleoli and the cell nuclei, which had greatly proliferated and exhibited irregular nuclear membranes. Advanced fibrosis was observed in central liver specimens of all groups. Marked alterations were also observed in the mitochondria and the mitochondrial cristae as well as in the bile canaliculi. Intracytoplasmic glycogen usually occurred densely clustered along the periphery of the cell. It may be concluded from the observations that both the total extract of atmospheric suspended particulate matter and the PAH fraction cause hematogenic damage to the liver following subcutaneous injection, a finding which cannot be interpreted as metastatic carcinoma.
Kindzierski, W.B.; Byrne-Lewis, C.; Probert, S.
The incomplete combustion of flare gases produces pollutants such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) which are cause for concern for public health. Some of the concerns relate to potential long-term cumulative health effects from exposure to hazardous air pollutants including benzene, styrene, naphthalene, and benzopyrene. This study demonstrated that several factors should be taken into account when considering the importance of flaring and human exposure to flare gas emissions. Most flare stacks are located in rural areas, but most time-availability studies have been done on urban populations where the majority of people spend their time indoors. It was recommended that more time-activity studies are needed to emphasize the behaviour of rural populations which are most susceptible to exposure from pollutants from flaring. It was concluded that higher indoor air concentrations exist for many VOCs and PAHs compared to outdoors, but in these instances, indoor sources are the major contributors to indoor air concentrations. It was recommended that health assessments of hazardous air pollutants emitted from gas flaring has to take into account the indoor setting and other background exposures in order to provide useful information for decision makers. 49 refs., 8 tabs., 1 fig
Full Text Available Air quality in Poland poses a serious threat for boththe society and the environment. According to the WHO research Poland is located on the 14th place as a country most contaminated by particulate matter (PM10. Equally health-threatening substances are ozone, PAH, nitrogen dioxide, sulfur oxide, carbon oxide and heavy metals. Long-lasting exposure to high concentrations of ozone and nitrogen dioxide may lead to many irreversible changes in lungs, pulmonary oedema and even death. The main PAH, which cumulates in the organism is benzopyrene. This substance has been described by the IARC as a the most cancerogenic factor. High concentration of sulfur oxide in the air may cause severe damage of upper respiratory tract, sulfur oxide contributes greatly also to the appearance of acid rain and is an ingredient of a London type smog. Heavy metals polluting the air are one of the most severe health threat for people, due to the ability to cumulate in the organism.
Zhou, Jun; Xu, Weizhong; Wong, Jonathan W. C.; Yong, Xiaoyu; Yan, Binghua; Zhang, Xueying; Jia, Honghua
Effects of different pretreatment methods on sludge dewaterability and polycyclic aromatic hydrocarbons (PAHs) degradation during petrochemical sludge anaerobic digestion were studied. Results showed that the total biogas production volume in the thermal pretreatment system was 4 and 5 times higher than that in the ultrasound pretreatment and in the control system, and the corresponding volatile solid removal efficiencies reached 28%, 15%, and 8%. Phenanthrene, paranaphthalene, fluoranthene, benzofluoranthene, and benzopyrene removal rates reached 43.3%, 55.5%, 30.6%, 42.9%, and 41.7%, respectively, in the thermal pretreatment system, which were much higher than those in the ultrasound pretreatment and in the control system. Moreover, capillary suction time (CST) of sludge increased after pretreatment, and then reduced after 20 days of anaerobic digestion, indicating that sludge dewaterability was greatly improved after anaerobic digestion. The decrease of protein and polysaccharide in the sludge could improve sludge dewaterability during petrochemical sludge anaerobic digestion. This study suggested that thermal pretreatment might be a promising enhancement method for petrochemical sludge solubilization, thus contributing to degradation of the PAHs, biogas production, and improvement of dewaterability during petrochemical sludge anaerobic digestion. PMID:26327510
Teo, Yin Nah; Wilson, James N.
We describe studies carried out in the DNA context to test how a common fluorescence quencher, dabcyl, interacts with oligodeoxynu-cleoside fluorophores (ODFs)—a system of stacked, electronically interacting fluorophores built on a DNA scaffold. We tested twenty different tetrameric ODF sequences containing varied combinations and orderings of pyrene (Y), benzopyrene (B), perylene (E), dimethylaminostilbene (D), and spacer (S) monomers conjugated to the 3′ end of a DNA oligomer. Hybridization of this probe sequence to a dabcyl-labeled complementary strand resulted in strong quenching of fluorescence in 85% of the twenty ODF sequences. The high efficiency of quenching was also established by their large Stern–Volmer constants (KSV) of between 2.1 × 104 and 4.3 × 105M−1, measured with a free dabcyl quencher. Interestingly, quenching of ODFs displayed strong sequence dependence. This was particularly evident in anagrams of ODF sequences; for example, the sequence BYDS had a KSV that was approximately two orders of magnitude greater than that of BSDY, which has the same dye composition. Other anagrams, for example EDSY and ESYD, also displayed different responses upon quenching by dabcyl. Analysis of spectra showed that apparent excimer and exciplex emission bands were quenched with much greater efficiency compared to monomer emission bands by at least an order of magnitude. This suggests an important role played by delocalized excited states of the π stack of fluorophores in the amplified quenching of fluorescence. PMID:19780115
Shabad, L M
A short history of a relatively new branch of cancer research, hygienic oncology, is reviewed. Occupational skin tumors (papillomas and even squamous-cell carcinoma) are described not only among chimney-sweepers, but also among the workers of petroleum refineries. Of 512 workers who had prolonged exposure to various petroleum products, 53.2% developed skin carcinoma. Occupational malignant tumors of the respiratory tract are observed among the workers of nickel industries. Workers who experienced prolonged exposure to asbestos had an increased incidence of lung and stomach cancer. To prevent occuptional cancer of the urinary bladder, such carcinogens as 2-napthylamine, 3,3-dichlorobenzidine, 3,3-dioxybenzidine, and para-amino-azobenzene were banned. Environmental pollution with the products of incomplete fuel combustion, especially with polycyclic aromatic carbohydrates constitutes a hazard to the urban population. The level of benzopyrene (BP) in soil samples taken in different localities averaged 5 microg/kg. Legislatively approved permissible concentrations of BP in the air are 0.1 microg/100 cubic meters, and in the water 0.005 microg/liter. 23 references.
Kulikowska-Karpińska, Elżbieta; Zdanowicz, Magdalena; Gałażyn-Sidorczuk, Małgorzata
Cigarette smoking is one of the most common habits of the modern world. According to a NATPOL PLU study, every third adult Pole is dependent on nicotine. Tobacco smoke contains about 5,000 components, of which over 1,000 are very toxic chemical substances (3,4-benzopyrene, heavy metals, free radicals, hydrogen cyanide, nitrogen oxides and N-nitrosamines). Exposure to tobacco smoke is an example of a complex, with a significant number of interactions. To assess the concentration of copper in the urine of smokers. Based on the results, an attempt was made to determine whether smoking can affect the level of copper in the body. The study involved 170 healthy volunteers, 99 smokers and 71 non-smokers (control group). The age of patients in both groups were in the range of 20-60 years. The mean age for men and women was 41 years. The average length of cigarette smoking was 18 years for women and 21 years for men, and the number of cigarettes smoked 1-40 ⁄ 24. The urine concentrations of Cu were determined by atomic absorption spectrometry (AAS) and serum creatinine kinetic method using a set of BIOLAB. Cu concentration in urine was expressed in mg / g creatinine. Smokers were found to have reduced levels of copper in the urine, depending on sex, age and brand of cigarettes. In male smokers, copper concentration in the urine was dependent on age and time of smoking, whereas among women this relationship was not observed. Cigarette smoking significantly influences the level of copper in the urine. Both female and male smokers showed reduced levels of copper in the urine, which may indicate its increased accumulation in the body. Excessive accumulation of copper is very dangerous since it may exhibit toxic effects towards many organs and systems.
A main source of pollution is the Nizhnii Tagil Integrated Iron and Steel Works (NTMK), whose share in the total emissions of harmful substances is very significant. Thus, in 1987 the mean annual dust content in the atmosphere of the city surpassed the maximum admissible concentrations 1.3 times, phenol 2 times, ammonia 2.5 times, benzopyrene 6 times. In 1988 an even higher content of harmful substances was noted. Reconstruction of the coke plant now underway has been called upon to ensure a significant improvement in the ecological conditions together with an overall increase in its technical level. Restoration of the existing capacity of the coke batteries at domestic coke plants is being accomplished according to two variants: first - relining of the batteries with retention of the existing dimensions or with a slight very limited increase, with modernization of the designs of the ovens and chemical departments, and also machines and equipment (technical refitting); second - withdrawal from operation of the existing batteries and construction of new higher capacity coke batteries in the plant area (reconstruction). From the standpoint of ecology and economy of capital investment it would be more expedient to restore capacity at NTMK according to the first variant. However, restoration here is being carried out according to the second variant with construction of coke batteries 9 and 10 in a new area with dry coke quenching. There are plans to decommission batteries 1-4. An analysis is given of the sources of pollution from the coke plant and measures are defined to reduce pollutants
The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs
Kiruthiga, P.V.; Pandian, S. Karutha; Devi, K. Pandima
PAHs are a ubiquitous class of environmental contaminants that have a large number of hazardous consequences on human health. An important prototype of PAHs, B(a)P, is notable for being the first chemical carcinogen to be discovered and the one classified by EPA as a probable human carcinogen. It undergoes metabolic activation to QD, which generate ROS by redox cycling system in the body and oxidatively damage the macromolecules. Hence, a variety of antioxidants have been tested as possible protectors against B(a)P toxicity. Silymarin is one such compound, which has high human acceptance, used clinically and consumed as dietary supplement around the world for its strong anti-oxidant efficacy. Silymarin was employed as an alternative approach for treating B(a)P induced damage and oxidative stress in PBMC, with an emphasis to provide the molecular basis for the effect of silymarin against B(a)P induced toxicity. PBMC cells exposed to either benzopyrene (1 μM) or silymarin (2.4 mg/ml) or both was monitored for toxicity by assessing LPO, PO, redox status (GSH/GSSG ratio), glutathione metabolizing enzymes GR and GPx and antioxidant enzymes CAT and SOD. This study also investigated the protective effect of silymarin against B(a)P induced biochemical alteration at the molecular level by FT-IR spectroscopy. Our findings were quite striking that silymarin possesses substantial protective effect against B(a)P induced oxidative stress and biochemical changes by restoring redox status, modulating glutathione metabolizing enzymes, hindering the formation of protein oxidation products, inhibiting LPO and further reducing ROS mediated damages by changing the level of antioxidant enzymes. The results suggest that silymarin exhibits multiple protections and it should be considered as a potential protective agent for environmental contaminant induced immunotoxicity.
Fossi, M. C.; Mori, G.; Baroni, D.; Bianchi, N. [Siena Univ., Siena (Italy). Dipt. di Scienze Ambientali
Toxicological risk assessment in the Orbetello lagoon (Grosseto, Italy) was carried by two approaches: biomonitoring based on estimates of residue levels in indicator species and biomarkers studies by which their responses to chemical and environmental stress were evaluated. In specimens of Carcinus aestuarii sampled in three differently impacted areas of the lagoon, levels of chlorinated hydrocarbons (DDTs, PCBs and HCBs), heavy metals (Pb, Cd and Hg) and 3 specific biomarkers (mixed function oxidase (MFO) induction, butyrylcholinesterase (BChE) inhibition and porphyrin accumulation) were measured. Overall results indicate that the lagoon is highly polluted. Of the three study sites, the highest concentrations of HCBs, DDTs and PCBs were observed in specimens from the mouth of the river Albegna, in which butyrylcholinesterase induction usually attributed to organophosphates (OPs) and carbamates (CBs), was considerable, as well. Specimens from S. Liberata, once known to be the most pristine site, showed clear signs of environmental degradation with high levels of Pb, Cd and organochlorine compounds, including PCBs. Benzopyrene monooxygenase (BPMO) values also seem to confirm such chemical stress. High levels of Hg and largely accumulated protoporphyrins and total porphyrins in C. aestuarii of the Sitoco site are only partially ascribed to the occurrence of Hg, as the presence of some unknown xenobiotics is likely. [Italian] In questo studio e' stato valutato il potenziale pericolo di composti inquinanti su una comunita' naturale della Laguna di Orbetello (Grosseto) utilizzando sia indagini di biomonitoraggio basate sulla stima dei livelli di residui in organismi bioindicatori, si una metodologia innovativa come lo studio di biomarkers (intendendo con cio' la valutazione delle risposte che un organismo genera nei confronti di uno strss chimico-ambientale). Su esemplari di Carcinus aestuarii, scelti come organismi bioindicatori e campionati in tre aree
Full Text Available Hamzah M Maswadeh,1 Ahmed N Aljarbou,1 Mohammed S Alorainy,2 Arshad H Rahmani,3 Masood A Khan3 1Department of Pharmaceutics, College of Pharmacy, 2Department of Pharmacology and Therapeutics, College of Medicine, 3College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia Abstract: Small unilamellar vesicles from camel milk phospholipids (CML mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC were prepared, and anticancer drugs doxorubicin (Dox or etoposide (ETP were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98% in liposomes (Lip prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP or DPPC-Lip-(Dox + ETP. Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the
Teo, Yin Nah; Kool, Eric T.
We describe studies aimed at testing whether oligomeric exciplex- and excimer fluorophores conjugated to DNA have the potential to act as donors for energy transfer by the Förster mechanism. Oligodeoxyfluorosides (ODFs) are composed of stacked, electronically interacting fluorophores replacing the bases on a DNA scaffold. The monomer chromophores in the twenty tetramer-length ODFs studied here include pyrene (Y), benzopyrene (B), perylene (E), dimethylaminostilbene (D), and a nonfluorescent spacer (S); these are conjugated in varied combinations at the 3’ end of a 14mer DNA probe sequence. In the absence of an acceptor chromophore, many of the ODF-DNAs show broad, unstructured long-wavelength emission peaks characteristic of excimer and exciplex excited states, similar to what has been observed for unconjugated ODFs. Although such delocalized excited states have been widely studied, we know of no prior report of their use in FRET. We tested the ability of the twenty ODFs to donate energy to Cy5 and TAMRA dyes conjugated to a complementary strand of DNA, with these acceptors oriented either at the near or far end of the ODF-conjugated probes. Results showed that a number of the ODF fluorophores exhibited relatively efficient energy transfer characteristic of the Förster mechanism, as judged by drops in donor emission quantum yield and fluorescence lifetime, accompanied by increases in intensity of acceptor emission bands. Excimer/exciplex bands in the donors were selectively quenched while shorter-wavelength monomer emission stayed relatively constant, consistent with the notion that the delocalized excited states, rather than individual fluorophores, are the donors. Interestingly, only specific sequences of ODFs were able to act as donors, while others did not, even though their emission wavelengths were similar. The new FRET donors possess large Stokes shifts, which can be beneficial for multiple applications. In addition, all ODFs can be excited at a single
Nishiwaki, Y.; Kawai, H.; Shono, N.; Fujita, S.; Matsuoka, H.; Fujiwara, S.; Hosoda, T.
In exploding an atomic bomb, in addition to ionizing radiation, strong non-ionizing radiation, such as infrared, ultraviolet light, visible light, electromagnetic pulse radiation, as well as heat and shock waves are produced. The survivors and those who visited Hiroshima immediately after the atomic bombing could have been subjected to a number of other possible noxious effects in addition to atomic radiation. Hospitals, laboratories, drugstores, pharmaceutical works, storehouses of chemicals, factories, etc. that were situated close to the hypocenter were all completely destroyed and various mutagenic, carcinogenic or teratogenic substances must have been released, many doctors, nurses and chemists were killed. There was no medical care and no food in the region of high dose exposure and the drinking water was contaminated. There would have been various possibilities of infection. Mental stress would also have been much higher in the survivors closer to the hypocenter. It is confusing which factor played a dominant role. In addition, there would be problems in accurately identifying the position of the exposed persons at the time of the atomic bombing and also in estimating the shielding factors. There may be considerable uncertainty in human memory under such conditions. It is also possible that there could have been a large storage of gasoline to be used for transportation of the army corps in Hiroshima. Therefore there is a possibility that various toxic substances, mutagenic or carcinogenic agents such as benzopyrene and other radiomimetic substances, chemical weapons (Yperit, Lewisite, etc.) could have been released from various facilities which were destroyed at the time of the atomic bombing. After the German surrender, in May 1945, it was reported in June, in Japan, that the USA might attempt landing on Japan mainland, and that they might be planning massive use of chemical weapons all over Japan on that occasion. Preparing for such case chemical officers
Schneider, K [comp.
Age-dependent carcinogenesis in humans has been proven with high probability for a number of substances investigated within one or several model systems. Sometimes, very high tumor incidence after short exposure time was observed. Extreme differences were found in some models. (A) Vinyl chloride, Maltoni et al.,1981: 6000 ppm, hepatic angiosarcoma incidence: - Exposure for 4 weeks, from day 1: 40.5 %, - exposure for 4 weeks, from week 13: 0%, - exposure for 52 weeks, from week 13: 22%. Hepatoma incidence: - Exposure for 4 weeks, from day 1: 47.6%, exposure for 4 weeks, from week 13: 0%, exposure for 52 weeks, from week 13: 1.7%. (B) Diethyl nitrosamine, Dyroff et al., 1986: (DEN + phenobarbital), hepatic carcinoma after exposure of rats for 6 weeks: - as from 4 weeks of age: 100% incidence, - as from 8 weeks of age: 0% incidence. (C) Benzopyrene, Vesselinovitch et al., 1975: Hepatic tumor incidence after single, parenteral administration to rats: - at day 1: males: 81%, females: 18%, - at day 42: males: 9%, females: 0%. As is shown by the study on vinyl chloride by Maltoni et al., the same exposure concentration may lead to higher tumor incidence in young animals after short exposure times than it does in long-term experiments with adult animals. Genetic toxicity was detected for all substances, except for saccharin. So it can be assumed that the mechanism of carcinogenesis has an essential influence on the age-dependence. This conclusion agrees well with mechanistic approaches. (orig./CB) [German] Fuer eine Reihe von Schadstoffen ist eine Altersabhaengigkeit der Kanzerogenese mit hoher Wahrscheinlichkeit in einem oder mehreren Modellsystemen gezeigt worden. Dabei wurden zum Teil bereits nach kurzer Expositionszeit sehr hohe Tumorausbeuten erzielt. Extreme Unterschiede wurden in folgenden Modellen beobachtet. (A) Vinylchlorid, Maltoni et al., 1981: 6000 ppm, Inzidenz Leberangiosarkome: - Exposition ueber 4 Wochen ab Tag 1: 40,5%, - Exposition ueber 4 Wochen ab 13
be used for transportation of the army corps in Hiroshima. Therefore there is a possibility that various toxic substances, mutagenic or carcinogenic agents such as benzopyrene and other radiomimetic substances could have been released from various facilities which were destroyed at the time of the atomic bombing. The enormous difference in dose rates between the atomic bombings and the radiation sources used for calibration experiments may also have some effect on some dosimetric systems or on some biological systems. Although it may be difficult to quantify some of these uncertainties, it is extremely important to keep all these uncertain factors in mind when analysing the atomic bomb effects of Hiroshima and Nagasaki. In Japan, medical X-ray examination is compulsory in schools, factories and companies. With certain diseases such as tuberculosis and some diseases of the lung and digestive systems extensive X-ray examinations may be conducted and periodically repeated. Survivors with a relatively low dose of high dose rate atomic bomb radiation must also have received some relatively low dose of low dose rate medical X-ray radiation. In other words, they must have received both high dose rate radiation and low dose rate radiation. There is a possibility of non-probabilistic uncertainties involved in estimation of the relative proportion of the two types of radiation and even greater uncertainties would be involved in the estimation of the organ doses. In these uncertainties both randomness and fuzziness may be involved.Under such situation it may be important to consider application of fuzzy theory for the analysis of cause-effect relationships. In exploding an atomic bomb, in addition to ionizing radiation, strong non-ionizing radiations, such as infrared, ultraviolet light, visible light, electromagnetic pulse radiation, as well as heat and shock waves are produced. Therefore, the possibility of the combined effects of all these direct factors and the indirect