Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer

Mycotoxin exposure and human cancer risk : a systematic review of epidemiological studies

In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to different mycotoxins with human cancer risk. Publications (2019 and earlier) of case–control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle–Ottawa scale. Animal, cross‐sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case–control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin‐contaminated foods and primary liver cancer risk was verified. Two case–control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case–control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose‐dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in‐depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence‐based public health strategies

Development and Validation of a New Bitumen Fume Generation System which Generates Polycyclic Aromatic Hydrocarbon Concentrations Proportional to Fume Concentrations

Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170°C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20°C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 µm at a fume concentration of 5 mg/m3 to 3.2 µm at 100 mg/m3. In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m3 range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road pavin

DNA adducts in fish following an oil spill exposure

On 12 December 1999, one third of the load of the Erika tanker, amounting to about 10,000 t crude oil flowed into sea waters close to the French Atlantic Coast. This oil contained polycyclic aromatic compounds (PAC) that are known to be genotoxic. Genotoxic effects induce DNA adducts formation, which can thus be used as pollution biomarkers. Here, we assessed the genotoxic impact of the “Erika” oil spill by DNA adducts detection in the liver of immature fishes (Solea solea) from four locations of the French Brittany coasts. Two months after the spill, a high amount of DNA adducts was found in samples from all locations, amounting to 92–290 DNA adduct per 109 nucleotides. Then total DNA adduct levels decreased to reach about 50 adducts per 109 nucleotides nine months after the spill. In vitro experiments using human cell cultures and fish liver microsomes evidence the genotoxicity of the Erika fuel. They also prove the formation of reactive species able to create DNA adducts. Furthermore, in vitro and in vivo DNA adducts fingerprints are similar, thus confirming that DNA adducts are a result of the oil spill

Development and validation of a new bitumen fume generation system which generates polycyclic aromatic hydrocarbon concentrations proportional to fume concentrations

Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170 degrees C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20 degrees C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 micro m at a fume concentration of 5 mg/m(3) to 3.2 micro m at 100 mg/m(3). In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m(3) range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road paving

Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium

The Black Aspergillus Species of Maize and Peanuts and Their Potential for Mycotoxin Production

The black spored fungi of the subgenera Circumdata, the section Nigri (=Aspergillus niger group) is reviewed relative to their production of mycotoxins and their effects on plants as pathogens. Molecular methods have revealed more than 18 cryptic species, of which several have been characterized as potential mycotoxin producers. Others are defined as benign relative to their ability to produce mycotoxins. However, these characterizations are based on in vitro culture and toxins production. Several can produce the ochratoxins that are toxic to livestock, poultry, and humans. The black aspergilli produce rots of grapes, maize, and numerous other fruits and grain and they are generally viewed as post-harvest pathogens. Data are review to suggest that black aspergilli, as so many others, are symptomless endophytes. These fungi and their mycotoxins contaminate several major grains, foodstuffs, and products made from them such as wine, and coffee. Evidence is presented that the black aspergilli are producers of other classes of mycotoxins such as the fumonisins, which are known carcinogenic and known prior investigations as being produced by the Fusarium species. Three species are identified in U.S. maize and peanuts as symptomless endophytes, which suggests the potential for concern as pathogens and as food safety hazards

Ochratoxin A in Portugal: A Review to Assess Human Exposure

In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on OTA research, a summary of the available data on OTA occurrence in food (cereals, bread, wine, meat) and biological fluids (blood, urine) is made. With this data, an estimation of intake is made to ascertain and update the risk exposure estimation of the Portuguese population, in comparison to previous studies and other populations