Polycyclic Aromatic Hydrocarbons in Foods: Biological Effects, Legislation, Occurrence, Analytical Methods, and Strategies to Reduce Their Formation.

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds comprised of carbon and hydrogen molecules in a cyclic arrangement. PAHs are associated with risks to human health, especially carcinogenesis. One form of exposure to these compounds is through ingestion of contaminated food, which can occur during preparation and processing involving high temperatures (e.g., grilling, smoking, toasting, roasting, and frying) as well as through PAHs present in the soil, air, and water (i.e., environmental pollution). Differently from changes caused by microbiological characteristics and lipid oxidation, consumers cannot sensorially perceive PAH contamination in food products, thereby hindering their ability to reject these foods. Herein, the occurrence and biological effects of PAHs were comprehensively explored, as well as analytical methods to monitor their levels, legislations, and strategies to reduce their generation in food products. This review updates the current knowledge and addresses recent regulation changes concerning the widespread PAHs contamination in several types of food, often surpassing the concentration limits deemed acceptable by current legislations. Therefore, effective measures involving different food processing strategies are needed to prevent and reduce PAHs contamination, thereby decreasing human exposure and detrimental health effects. Furthermore, gaps in literature have been addressed to provide a basis for future studies.

Investigation of Environmental Pollutant-Induced Lung Inflammation and Injury in a 3D Coculture-Based Microfluidic Pulmonary Alveolus System.

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.

Targeting glutathione with the triterpenoid CDDO-Im protects against benzo-a-pyrene-1,6-quinone-induced cytotoxicity in endothelial cells.

Epidemiological studies have exhibited a strong correlation between exposure to air pollution and deaths due to vascular diseases such as atherosclerosis. Benzo-a-pyrene-1,6-quinone (BP-1,6-Q) is one of the components of air pollution. This study was to examine the role of GSH in BP-1,6-Q mediated cytotoxicity in human EA.hy96 endothelial cells and demonstrated that induction of cellular glutathione by a potent triterpenoid, CDDO-Im (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole), protects cells against BP-1,6-Q induced protein and lipid damage. Incubation of EA.hy926 endothelial cells with BP-1,6-Q caused a significant increase in dose-dependent cytotoxicity as measured by LDH release assay and both apoptotic and necrotic cell deaths as measured by flow cytometric analysis. Incubation of EA.hy926 endothelial cells with BP-1,6-Q also caused a significant decrease in cellular GSH levels. The diminishment of cellular GSH by buthionine sulfoximine (BSO) potentiated BP-1,6-Q-induced toxicity significantly suggesting a critical involvement of GSH in BP-1,6-Q induced cellular toxicity. GSH-induction by CDDO-Im significantly protects cells against BP-1,6-Q induced protein and lipid damage as measured by protein carbonyl (PC) assay and thiobarbituric acid reactive substances (TBARS) assay, respectively. However, the co-treatment of cells with CDDO-Im and BSO reversed the cytoprotective effect of CDDO-Im on BP-1,6-Q-mediated lipid peroxidation and protein oxidation. These results suggest that induction of GSH by CDDO-Im might be the important cellular defense against BP-1,6-Q induced protein and lipid damage. These findings would contribute to better understand the action of BP-1,6-Q and may help to develop novel therapies to protect against BP-1,6-Q-induced atherogenesis.

Autophagy Activation by Crepidiastrum Denticulatum Extract Attenuates Environmental Pollutant-Induced Damage in Dermal Fibroblasts.

Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope. Crepidiastrum denticulatum (CD) extract treated cells showed the highest autophagic vacuole formation in the non-cytotoxic range. The phosphorylation of adenosine monophosphate kinase (AMPK), but not the inhibition of mammalian target of rapamycin (mTOR), was observed by CD-extract treatment. Its anti-pollution effects were further evaluated with model compounds, benzo[a]pyrene (BaP) and cadmium chloride (CdCl2), and a CD extract treatment resulted in both the protection of cytotoxicity and a reduction of proinflammatory cytokines. These results suggest that the autophagy activators can be a new protection regimen for anti-pollution. Therefore, CD extract can be used for anti-inflammatory and anti-pollution cosmetic ingredients.

Taxifolin ameliorates Benzo[a]pyrene-induced lung injury possibly via stimulating the Nrf2 signalling pathway.

Benzo[a]pyrene, an environmental contaminant as well as a mutagen is widely found in cigarette smoke, automobile exhaust particles among other sources. The present study underlines the protective effect of Taxifolin on B[a]P induced lung injury in male Swiss Albino Mice by analyzing the activity/level of various pro and anti-oxidant parameters, Inflammatory markers, Phase II enzyme, as well as lung histology. Taxifolin was administered orally to mice at either dose of 20 or 40 mg/kg body weight for 14 days and then challenged with a single dose of B[a]P (125 mg/kg body weight by oral gavage) on the 14th day. Our results show treatment with B[a]P leads to increased activity/level of CYP450R, EH, pro-inflammatory proteins, as well as lipid peroxidation and reduce level/activity of anti-oxidant molecules while Taxifolin treatment shows ameliorative effect. Administration of B[a]P also leads to decrease in expression of ROS sensitive factor Nrf2 and its downstream target NQO1,HO-1,SOD while Taxifolin treated animals showed a very high level of expression of Nrf2,NQO1,HO-1,SOD. Since Nrf2 plays central role in providing resistance to oxidative stress and also suppresses inflammation by inhibiting NF-κB,we concluded Taxifolin suppresses oxidative stress and inflammation in B[a]P induced lung injury possibly via stimulating the Nrf2 signaling pathway.

Activation of MAPK and Cyclin D1/CDK4 in Malignant Transformation of Human Embryonic Lung Fibroblasts Induced by Silica and Benzopyrene.

OBJECTIVE: Silica and Benzo(a)pyrene are listed as carcinogens. This study aims to explore Cyclin D1, CDK4 and difference of cell cycle adjusted by MAPK signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts. METHODS: Activity of the subfamily (ERK, p38 and JNK) of mitogen-activated protein kinase (MAPK), cyclin D1 and CDK4 (cyclin dependent kinase) were evaluated using Human embryonic lung fibroblast (HELF) purchased from the cell room, basic research institute, Chinese Academy of Medical Sciences. The expression of cyclin D1 and CDK4 (cyclin dependent kinase) were measured in silica and B(a)P induced malignant using Western blot (WB) assay. RESULT: P-ERK and P-JNK expression increased significantly (P<0.01), while CDK4 and P-p38 expression decreased (P<0.01, P<0.05) in silica-induced malignant transformation cells compared with the control group. P-ERK, P-JNK and Cyclin D1 expression increased (P<0.01, P<0.01, P<0.05) in B(a)P-induced group compared with the control group. P-ERK and P-JNK expression decreased (P<0.01), while P-p38, Cyclin D1 and CDK4 expression increased (P<0.05, P<0.05, P<0.01) in B(a)P-induced group compared with the silica-induced group. CONCLUSION: MAPK and cyclin D1/CDK4 activation expressed differently in human embryo lung fibroblasts malignant transformation induced by silica and benzopyrene.

[The content of benzpyrene in different areas of a megapolis].

The content of benzpyrene was studied in the ambient air of the mixed, residential, and industrial zones of Tashkent. There was no excess of the maximum allowable concentrations (MAC) of this substance in the ambient air of mixed and residential zones. There were 1.5-2-fold excesses in the MAC of benzpyrene in the places where apartment houses were contiguous with industrial enterprises and highways and 2.5-3-fold excesses in the ambient air of an industrial zone.

Strategies for Avoiding Benzopyrone Hepatotoxicity in Lymphedema Management-The Role of Pharmacogenetics, Metabolic Enzyme Gene Identification, and Patient Selection.

INTRODUCTION: Benzopyrones are plant-derived chemicals which have an evidenced degree of clinical efficacy in lymphedema management indicated in past trials. Unfortunately, in some of these cases idiosyncratic hepatotoxicity have been documented in a minority of patients. This review aims to tackle the problem of benzopyrone (particularly coumarin) toxicity by considering their metabolic pathways and identifying relevant alleles needed to take a targeted pharmacogenetic approach in its future use. METHODS AND RESULTS: The nontoxic 7-hydroxylation and the toxic heterocyclic "ring-splitting" epoxidation pathways are the two main detoxification pathways in the hepatometabolism of coumarin, the former catalyzed by CYP2A6 and the latter by possibly CYP1A and CYP2E. Acetaldehyde dehydrogenase (ALDH) clears toxic aldehyde intermediates. CYP2A6 polymorphism screening methods, including genotyping, by real-time polymerase chain reaction and chromatography-mass spectroscopy functional metabolite assays; efficiency of these techniques are continually improving. ALDH polymorphisms have also been implicated, with clinically viable screening tests, rapid genotyping, and sensitive questionnaires already available for ALDH2*1/ALDH2*2. Dysfunctional polymorphisms of the above genes and others are significantly more prevalent in Eastern Asian populations, uncommon in Caucasian populations. The role of other enzymes/genes in the pathway is yet to be clarified. CONCLUSION: Although screening techniques are becoming increasingly clinically feasible, uncertainty remains on the link between the genotype, metabolic phenotype, and the exact gene products involved. These must be elucidated further before a targeted pharmacogenomic approach is fully viable. In the meantime, treatment should be avoided in those with vulnerable familial and ethnic descents if used.

Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents.

Benzyl isothiocyanate, beta-naphthoflavone, coumarin, alpha-angelicalactone, disulfiram, indole-3-carbinol and indole-3-acetonitrile induced increased glutathione (GSH) S-transferase activity in the liver and small intestine in female ICR/Ha mice. All seven compounds are inhibitors of chemical carcinogenesis. In additional work, several dietary constituents increased GSH S-transferase activity. Consumption of diets containing dried powdered preparations of brussels sprouts, cabbage, coffee beans, or tea leaves resulted in increased GSH S-transferase activity. Mice fed an unrefined diet (Purina Rat Chow) had a higher GSH S-transferase activity than those fed a semipurified diet. The results of the present study indicated that the composition of the diet can alter the activity of an important enzyme system having the capacity to detoxify chemical carcinogens.

Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in combustion products of organic matter, including cigarette smoke. Metabolically activated diol epoxides of these compounds, including benzo[a]pyrene diol epoxide (B[a]PDE), have been suggested as causative agents in the development of lung cancer. We previously mapped the distribution of B[a]PDE adducts within the p53 tumor suppressor gene (also known as TP53), which is mutated in 60% of human lung cancers, and found that B[a]PDE adducts preferentially form at lung cancer mutational hotspots (codons 154, 157, 158, 245, 248, and 273). Other PAHs may be important in lung cancer as well. METHODS: Here we have mapped the distribution of adducts induced by diol epoxides of additional PAHs: chrysene (CDE), 5-methylchrysene (5-MCDE), 6-methylchrysene (6-MCDE), benzo[c]phenanthrene (B[c]PDE), and benzo[g]chrysene (B[g]CDE) within exons 5, 7, and 8 of the p53 gene in human bronchial epithelial cells. RESULTS: CDE exposure produced only low levels of adducts. Exposure of cells to the other activated PAHs resulted in DNA damage patterns similar to those previously observed with B[a]PDE but with some distinct differences. 5-MCDE, 6-MCDE, B[g]CDE, and B[c]PDE efficiently induced adducts at guanines within codons 154, 156, 157, 158, and 159 of exon 5, codons 237, 245 and 248 of exon 7, and codon 273 of exon 8, but the relative levels of adducts at each site varied for each compound. B[g]CDE, B[c]PDE, and 5-MCDE induced damage at codon 158 more selectively than 6-MCDE or B[a]PDE. The sites most strongly involved in PAH adduct formation were also the sites of highest mutation frequency (codons 157, 158, 245, 248, and 273). CONCLUSION: The data suggest that PAHs contribute to the mutational spectrum in human lung cancer.

Metabolic activation of benzo(a)pyrene and binding to DNA in cultured human bronchus.

Human bronchus is one target site for the carcinogenic action of tobacco smoke, which contains chemical carcinogens, including benzo(a)pyrene. Human bronchi were obtained from surgery or "immediate" autopsy and then cultured in a chemically defined medium. The cultured bronchi were exposed to either benzo(a)pyrene or its metabolites, and their levels of binding to DNA were measured. One of the benzo(a)pyrene metabolites. (-)-trans-7,8-diol, is more active in binding to DNA than benzo(a)pyrene and several of its metabolites, including (-)-trans-4,5-diol, (-)-trans-9,10-diol, and phenols. The predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol is found by high-pressure liquid chromatographic analysis to be the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound to DNA in human bronchus.

Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis in vitro.

Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 µmol/L), Al (mal)3 groups (50, 100, 400 µmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 µM BaP or 50 µM Al (mal)3 was mildly toxic, and we selected 10 µM BaP+50 µM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis.

Cutaneous chemical carcinogenesis: past, present, and future.

Skin tumors chemically induced in mice have provided an important experimental model for studying carcinogenesis and for bioassaying carcinogenic agents. The information obtained from this model suggests that the events leading to tumor formation can be divided into at least two stages, initiation and promotion. A single small dose of carinogen produces initiation which appears to be irreversible. These initiating agents may have to be metabolically activated and can interact with cellular macromolecules. The extent to which they bind to DNA correlates well with their carcinogenicity. Increased DNA replication at the time of or during the first day after these agents have been applied appears to enhance carcinogenesis. Unlike initiation, promotion appears to be reversible and the promoting agents must be applied repeatedly before tumors are formed. Promoters interact with membranes, stimulate and alter genetic expression, and increase the rate of cell proliferation. The knowledge gained from these studies in mouse skin has immeasurably helped the entire field of chemical carcinogenesis. But efforts to determine the cellular and molecular mechanisms involved in the carcinogenic process, particularly in the skin, have been hampered by the difficulties of working on whole animals and by the special problems associated with the biologic and biochemical methods required for this target organ. Such problems, however, can be solved by the use of cell cultures of mouse epidermis which can metabolize and bind carcinogens just as is done in vivo. The fact that epidermal cells in vitro proliferate synchronously should facilitate the study of the relation between the cell cycle and carcinogenesis. These cells repair chemically induced DNA damage by at least two mechanisms, excision repair and base-specific repair. When epidermal cells in vitro are exposed to promoting agents, a proliferative response analogous to that in vivo is elicited, apparently mediated through control of polyamine metabolism. Neoplastic transformation has been induced in these cultures by known skin carcinogens.

Age-related negative associations between parameters of cytogenetic damage and ex vivo (+/-)-anti-benzo(a)pyrene diolepoxide-induced unscheduled DNA synthesis in smoking humans.

Chemical or physical modification of DNA may cause an increase in genomic mutations or other genetic alterations, which may ultimately result in the onset of cancer. To avoid these deleterious effects of DNA damage, humans possess DNA repair mechanisms. Decreased DNA repair, induced ex vivo by UV light or ionizing radiation in human peripheral blood lymphocytes (PBLs), has been associated with aging. The aim of this study was to investigate whether repair of DNA damage, after ex vivo exposure of PBLs obtained from smokers (n = 20) to (+/-)-anti-benzo(a)pyrene diolepoxide [(+/-)-anti-BPDE], which is a mixture of reactive metabolites from the environmental carcinogen benzo(a)pyrene, is also associated with age. Furthermore, age-related associations between ex vivo (+/-)-anti-BPDE-induced DNA repair and the frequency of endogenous cytogenetic damage (sister chromatid exchange frequencies and micronuclei frequencies) in PBLs were evaluated. A statistically significant negative association was observed between ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and age of the donors. Also, parameters of endogenous lymphocytic cytogenetic damage were negatively associated with ex vivo (+/-)-anti-BPDE-induced unscheduled DNA synthesis and positively associated with age in this population. It is concluded that, with increasing age, a decrease in lymphocytic excision repair capacity may be responsible for increased lymphocytic DNA damage in smokers.

Determination of point mutational spectra of benzo[a]pyrene-diol epoxide in human cells.

The primary goal of our research consists of developing means sufficiently sensitive to allow assessment of human exposure to environmental carcinogens. We describe here a new approach for analyzing point mutational spectra and a test for its validity and precision using cultured human cells exposed to high doses of environmental carcinogens. The approach in its present form includes a) treatment of independent large cultures of human cells with a carcinogen, b) selection of mutant cells en masse by 6-thioguanine resistance, c) amplification of sequences of interest directly from 6TGR cells using high-fidelity polymerase chain reaction, and d) separation of mutant sequences from nonmutant sequences using denaturing gradient gel electrophoresis. We report use of this protocol to observe induced mutational spectra in exon 3 of the hprt gene in cultured human cells by benzo[a]pyrene-diol epoxide (BPDE), an active form of the widely distributed environmental carcinogen benzo[a]pyrene. BPDE induced predominantly G to T transversions within this target sequence. The variation of the frequency of the mutations among independent cultures is consistent with the interpretation that each of them corresponds to a hotspot.

Application of tumor, bacterial and parasite susceptibility assays to study immune alterations induced by environmental chemicals.

Model systems to study the effects of chemicals of environmental concern on bacterial and parasitic diseases as well as the immunosurveillance and destruction of transplantable tumor cells were described and evaluated. Studies were conducted in female B6C3F1 mice following adult or pre/postnatal exposure to several prototype chemicals. The prototype chemicals employed included the synthetic estrogen diethylstilbestrol (DES), the polycyclic aromatic hydrocarbon benzo(a)pyrene (B[a]P), and the carcinogenesis promoting agent 12-0-tetradecanoyl-phorbol-13-0-acetate (TPA). The host resistance models employed depend primarily on functional thymus-dependent immunity, although humoral immunity is suggested to have a role in the parasite model as well. These models include: subcutaneous challenge with a dose of PYB6 tumor cell causing a 10-20% incidence (TD(10-20)) of tumor; intravenous challenge with B16 melanoma cells; challenge with a dose of Listeria monocytogenes causing a 10-20% incidence of mortality (LD(10-20)); challenge with a dose of E. coli lipopolysaccharide endotoxin causing a 10-20% incidence of lethality (LD(10-20)); and challenge with larvae of Trichinella spiralis for parasite expulsion kinetic studies. Increased mortality was observed following Listeria monocytogenes challenge in DES-exposed mice. B(a)P and TPA exposure did not alter host resistance to this organism. The increased mortality observed following DES was associated with a significant increase in the number of viable Listeria in the spleens and livers at 4 days, a time when T-cell immunity is thought to be expressed, but bacterial counts were similar to control mice at day 1, a time when MPhi are thought to exert their greatest effect. These data suggest that the increased Listeria susceptibility found following DES exposure may result from a T-cell defect, although the intracellular killing capacity of DES-treated Mvarphi's has not been well examined. Tumor susceptibility studies following challenge with 5 x 10(3) viable syngeneic PYB6 tumor cells revealed that nontreated adult B6C3F1 mice resisted tumor formation, with only a 10-20% incidence of tumor formation. In contrast, mice exposed to DES or TPA as adults had a tumor frequency of from 70-100% following TPA and up to 90% following DES exposure. In all cases the tumors were progressive and resulted in death. B(a)P did not alter the frequency of tumor incidence from controls in this model. Preliminary data, using the B16 melanoma intravenous challenge model and (125)IUdR to quantitate tumor mass revealed this model was sensitive to non-specifically activated macrophage kill. DES treated mice with activated macrophages did not demonstrate increased tumor mass, while mice exposed to TPA or the potent immunosuppressive agent cyclophosphamide had a significantly increased tumor mass in their lungs. Expulsion of Trichinella spiralis adults from the gut also apparently required functional T-cells and possibly some element of humoral immunity. Mice exposed to DES and B(a)P exhibited increased numbers of adult worms in the gut at day 14. Sensitivity to gram-negative endotoxin (LPS) was apparently increased following exposure to DES or B(a)P. These data suggest that the detoxification of LPS is related to an intact Mvarphi population. The data presented here demonstrate the sensitivity of the host resistance assay panel proposed for detecting immune alteration. Alteration of T-cell function appeared to correlate with increased susceptibility to bacterial and tumor cell challenge.

Acceleration of the development of benzopyrene-induced skin cancer in mice by microwave radiation.

Development and growth of skin cancer may be affected by various physical and chemical factors present in human environment. Of these factors electromagnetic radiation of radio- and microwave spectra are among the most common. In the present study Balb/c mice were exposed to chemical carcinogen, 3,4-benzopyrene, painted on the skin every 2nd day for a total of 6 months, and simultaneously irradiated with athermal (5 mW/cm2) or subthermal (15 mW/cm2) doses of 2,450 MHz microwaves. The other group of animals was preirradiated with microwaves at 10 mW/cm2 power level for 1, 2, or 3 months and then treated with benzopyrene, as above. Control mice were exposed for 6 months to benzopyrene, resulting in the development of baso- or spinocellular skin carcinoma within approximately 9 months, and sham-irradiated with microwaves. The growth of the tumour was assessed according to a self-designed 7-range macroscopic scale, supported by microscopical examinations of skin sections. All protocols of microwave irradiations resulted in a significant acceleration of the development of benzopyrene-induced skin cancer and in shortening of life span of the tumour-bearing hosts. This effect seemed to be dose-dependent since subthermal doses (15 mV/cm2) and longer (3 months) expositions to microwaves were more efficient as compared to athermal doses (5 mW/cm2) and shorter preirradiations. In addition, low-level, long-lasting exposure to microwaves led to a marked suppression of delayed hypersensitivity of mice treated with benzopyrene, as assessed by their reactivity to dinitrofluorbenzene (DNFB). It is suggested that the observed co-carcinogenic effect of microwave radiation may, at least in part, result from the inhibitory action of microwaves on cellular immune reactions of exposed animals.

Genotoxicity of aerosol extracts. Some methodological aspects and the contribution of urban and industrial locations.

The genotoxicity of aerosol extracts was investigated with the Ames test and an SCE test in vitro. In addition to experiments to evaluate current techniques, a so-called gradient study was carried out in an industrialized part of The Netherlands to obtain insight into the contribution of urban and industrial locations to the genotoxicity of aerosol extracts. The influence of variations in the sampling was investigated. The results indicate that moderate variations in the volume of air sampled per unit of time and of the duration of the sampling period do not have a great influence on the effect measured. Experiments with filters impregnated with 14C-labelled benzo[a]pyrene showed that this compound is converted during sampling into directly active mutagens; no evaporation occurred. The results of experiments to evaluate the extraction procedure indicated that an 8-h Soxhlet extraction with methanol is better than, or as good as, Soxhlet extraction with other solvents. The gradient study showed that the aerosol downwind from industrial/urban areas exerted a reproducibly stronger effect in the Ames test and the SCE test when compared with aerosol from sea air.

[Effects of air pollution on health]. / Effets de la pollution atmosphérique sur la santé

Air pollution is composed of a particulate phase and a gaseous phase. The particulate phase, consisting of dust and aerosols, is the vehicle of toxic pollutants, transporting them into the respiratory tract. The irritants (sulphur dioxide, nitrogen oxides, aldehydes, and hydrocarbons) are the most important pollutants as regards health; the mucous membranes of the eyes and the respiratory tract are mostly affected. Other substances penetrate into the organism where they can develop actions harmful to various organs (carbon monoxide), generate cancer (polyaromatic hydrocarbons) or attack enzymatic systems (lead). Epidemiologic studies have revealed that populations exposed to high degrees of air pollution show increased mortality, which is mainly due to illnesses of the respiratory tract. Atmospheric pollution can also cause sensations of unpleasantness due to irritations of the eyes and the respiratory tract, bad odours, and the impairment of visibility and sunlight.

[Etiology of lung cancer in workers of graphite industry]. / Ob étiologii raka legkogo u rabochikh proizvodstva grafitovykh izdelii.

Carcinogenic hazards for workers of certain plants of steel, asbestos, oil-producing, oil-refining and chemical industries were studied. Potential carcinogenic hazards for workers of graphite industry conditioned mainly by coke and graphite dust adsorbed polycyclic hydrocarbons, particularly, benzo(a)pyrene made the case for cancer epidemiologic studies which were carried out at some of those plants in the 70s. Exposure to polycyclic hydrocarbons adsorbed on industrial dust was shown to significantly increase the incidence of lung cancer.