BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

• MeSH
• azbest * toxicita   MeSH
• chrom toxicita   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• nádory plic * chemicky indukované   epidemiologie   MeSH
• oxid křemičitý toxicita   MeSH
• plíce MeSH
• polycyklické aromatické uhlovodíky * toxicita   MeSH
• pracovní expozice * MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azbest * MeSH
• chrom MeSH
• chromium hexavalent ion MeSH Prohlížeč
• karcinogeny MeSH
• oxid křemičitý MeSH
• polycyklické aromatické uhlovodíky * MeSH

Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi. The most toxic among them is Aflatoxin B1 (AFB1) which is known to have genotoxic, immunotoxic, teratogenic, carcinogenic, and mutagenic toxic effects (amongst others). The mechanisms responsible for its toxicity include the induction of oxidative stress, cytotoxicity, and DNAdamage. Studies have found that natural anti-oxidants can reduce the damage that AFB1 inflicts on the body by alleviating oxidative stress and inhibiting the biotransformation of AFB1. Therefore, this review outlines the latest progress in research on the use of natural anti-oxidants as antidotes to aflatoxin poisoning and their detoxification mechanisms. It also considers the problems that may possibly arise from their use and their application prospects. Our aim is to provide a useful reference for the prevention and treatment of AFB1 poisoning.

• Klíčová slova
• AFB1, Detoxification, Natural anti-oxidant,
• MeSH
• aflatoxin B1 * metabolismus   otrava   toxicita   MeSH
• antidota * farmakologie   MeSH
• antioxidancia * farmakologie   MeSH
• II. fáze biotransformace * MeSH
• karcinogeny metabolismus   toxicita   MeSH
• kur domácí MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aflatoxin B1 * MeSH
• antidota * MeSH
• antioxidancia * MeSH
• karcinogeny MeSH

The plant extract aristolochic acid (AA), containing aristolochic acids I (AAI) and II (AAII) as major components, causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases associated with upper urothelial cancer. Recently (Chemical Research in Toxicology 33(11), 2804-2818, 2020), we showed that the in vivo metabolism of AAI and AAII in Wistar rats is influenced by their co-exposure (i.e., AAI/AAII mixture). Using the same rat model, we investigated how exposure to the AAI/AAII mixture can influence AAI and AAII DNA adduct formation (i.e., AA-mediated genotoxicity). Using 32P-postlabelling, we found that AA-DNA adduct formation was increased in the livers and kidneys of rats treated with AAI/AAII mixture compared to rats treated with AAI or AAII alone. Measuring the activity of enzymes involved in AA metabolism, we showed that enhanced AA-DNA adduct formation might be caused partially by both decreased AAI detoxification as a result of hepatic CYP2C11 inhibition during treatment with AAI/AAII mixture and by hepatic or renal NQO1 induction, the key enzyme predominantly activating AA to DNA adducts. Moreover, our results indicate that AAII might act as an inhibitor of AAI detoxification in vivo. Consequently, higher amounts of AAI might remain in liver and kidney tissues, which can be reductively activated, resulting in enhanced AAI DNA adduct formation. Collectively, these results indicate that AAII present in the plant extract AA enhances the genotoxic properties of AAI (i.e., AAI DNA adduct formation). As patients suffering from AAN and BEN are always exposed to the plant extract (i.e., AAI/AAII mixture), our findings are crucial to better understanding host factors critical for AAN- and BEN-associated urothelial malignancy.

• Klíčová slova
• Balkan endemic nephropathy, DNA adducts, NAD(P)H:quinone oxidoreductase 1, aristolochic acid I, aristolochic acid II, aristolochic acid nephropathy, aristolochic acid-mediated carcinogenesis, cytochrome P450, genotoxicity,
• MeSH
• adukty DNA metabolismus   MeSH
• DNA nádorová metabolismus   MeSH
• karcinogeneze * chemicky indukované   metabolismus   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• kyseliny aristolochové toxicita   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adukty DNA MeSH
• aristolochic acid B MeSH Prohlížeč
• aristolochic acid I MeSH Prohlížeč
• DNA nádorová MeSH
• karcinogeny MeSH
• kyseliny aristolochové MeSH

Sphingolipids (SLs), glycosphingolipids (GSLs), and eicosanoids are bioactive lipids, which play important roles in the etiology of various diseases, including cancer. However, their content and roles in cancer cells, and in particular in the exosomes derived from tumor cells, remain insufficiently characterized. In this study, we evaluated alterations of SL and GSL levels in transformed cells and their exosomes, using comparative HPLC-MS/MS analysis of parental human bronchial epithelial cells HBEC-12KT and their derivative, benzo[a]pyrene-transformed HBEC-12KT-B1 cells with the acquired mesenchymal phenotype. We examined in parallel SL/GSL contents in the exosomes released from both cell lines. We found significant alterations of the SL/GSL profile in the transformed cell line, which corresponded well with alterations of the SL/GSL profile in exosomes derived from these cells. This suggested that a majority of SLs and GSLs were transported by exosomes in the same relative pattern as in the cells of origin. The only exceptions included decreased contents of sphingosin, sphingosin-1-phosphate, and lactosylceramide in exosomes derived from the transformed cells, as compared with the exosomes derived from the parental cell line. Importantly, we found increased levels of ceramide phosphate, globoside Gb3, and ganglioside GD3 in the exosomes derived from the transformed cells. These positive modulators of epithelial-mesenchymal transition and other pro-carcinogenic processes might thus also contribute to cancer progression in recipient cells. In addition, the transformed HBEC-12KT-B1 cells also produced increased amounts of eicosanoids, in particular prostaglandin E2. Taken together, the exosomes derived from the transformed cells with specifically upregulated SL and GSL species, and increased levels of eicosanoids, might contribute to changes within the cancer microenvironment and in recipient cells, which could in turn participate in cancer development. Future studies should address specific roles of individual SL and GSL species identified in the present study.

• Klíčová slova
• eicosanoids, exosomes, glycosphingolipid, in vitro cell transformation, sphingolipid,
• MeSH
• benzopyren toxicita   MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• exozómy metabolismus   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• nádorová transformace buněk * MeSH
• respirační sliznice účinky léků   metabolismus   MeSH
• sfingolipidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzopyren MeSH
• karcinogeny MeSH
• sfingolipidy MeSH

Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered.

• MeSH
• akutní selhání jater chemicky indukované   metabolismus   patologie   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední LEW MeSH
• sexuální faktory MeSH
• testosteron metabolismus   MeSH
• thioacetamid toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• karcinogeny MeSH
• testosteron MeSH
• thioacetamid MeSH

OBJECTIVES: Acrylamide is a toxic compound that can be found it both occupational and non-occupational environments. This study focuses on its sources and health effects of its exposure. METHODS: Adverse effects of acrylamide, especially carcinogenic, genotoxic, and teratogenic were reported in many studies conducted on animals. Neurotoxicity was reported in workers exposed to acrylamide in the occupational environment. Another important source of populations' exposure to acrylamide is their nutrition. RESULTS: This study focuses on humans' exposure to acrylamide from various sources and its harmful effects on their health. CONCLUSIONS: Dietary intake of acrylamide, as well as occupational exposure, cigarette smoking, cosmetics usage and other environmental sources could have a significant effect on human health.

• Klíčová slova
• acrylamide, carcinogen, neurotoxin, occupational exposure, polyacrylamide,
• MeSH
• akrylamid * toxicita   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• nutriční stav účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• pracovní expozice * škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamid * MeSH
• karcinogeny MeSH

Ethylene oxide (EO), a carcinogenic chemical used as an industrial intermediate and sterilant, forms covalent adducts with DNA and proteins. The adduct with N-terminal valine [N-(2-hydroxyethyl)-l-valine, HEV] in blood protein globin has been employed as a principal biomarker of cumulative exposures to EO. However, as sampling of blood is inconvenient in routine occupational health practice, a non-invasive alternative to globin analysis has been investigated. Following identification of N-(2-hydroxyethyl)-l-valyl-l-leucine (HEVL) as ultimate cleavage product of EO-adducted globin excreted in the rat urine, here we report for the first time on the presence of HEVL in the urine of humans. In 18 sterilization workers, urinary HEVL ranged from 0.67 to 11.98 μg/g creatinine (mean ± SD: 5.04 ± 3.14 μg/g creat) and correlated with HEV: HEVL (μg/g creat) = 0.833 HEV (nmol/g globin) + 1.19 (R2 = 0.45). As unexpectedly high levels of urinary HEVL were found also in controls (mean ± SD: 0.97 ± 0.37 μg/g creat, n = 32), HEVL is not proposed for the accurate assessment of sub-ppm exposures to EO. On the other hand, non-invasive sampling and facile work-up procedure predetermine HEVL for screening purposes to identify subjects approaching to or exceeding occupational exposure limit for EO (1.8 mg/m3) to be re-examined by the more sensitive reference analysis for HEV.

• Klíčová slova
• Biological monitoring, Ethylene oxide, Globin adducts, Occupational exposure, Urinary dipeptidic adducts,
• MeSH
• biologické markery moč   MeSH
• biologický monitoring metody   MeSH
• dospělí MeSH
• ethylenoxid moč   MeSH
• karcinogeny toxicita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pracovní expozice škodlivé účinky   MeSH
• valin moč   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• ethylenoxid MeSH
• karcinogeny MeSH
• valin MeSH

Health-threatening consequences of carcinogen exposure are mediated via occurrence of electrophiles or reactive oxygen species. As a result, the accumulation of biomolecular damage leads to the cancer initiation, promotion or progression. Accordingly, there is an association between lifestyle factors including inappropriate diet or carcinogen formation during food processing, mainstream, second or third-hand tobacco smoke and other environmental or occupational carcinogens and malignant transformation. Nevertheless, increasing evidence supports the protective effects of naturally occurring phytochemicals against carcinogen exposure as well as carcinogenesis in general. Isolated phytochemicals or their mixtures present in the whole plant food demonstrate efficacy against malignancy induced by carcinogens widely spread in our environment. Phytochemicals also minimize the generation of carcinogenic substances during the processing of meat and meat products. Based on numerous data, selected phytochemicals or plant foods should be highly recommended to become a stable and regular part of the diet as the protectors against carcinogenesis.

• Klíčová slova
• Antioxidant, Carcinogens, Chemoprevention, Detoxification, Dietary phytochemicals, Metabolic activation, Scavenging effect,
• MeSH
• antikarcinogenní látky farmakologie   terapeutické užití   MeSH
• fytonutrienty farmakologie   terapeutické užití   MeSH
• karcinogeneze účinky léků   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• potraviny škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikarcinogenní látky MeSH
• fytonutrienty MeSH
• karcinogeny MeSH

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

• MeSH
• azbest toxicita   MeSH
• karcinogeny * toxicita   MeSH
• lidé MeSH
• nádory hrtanu * chemicky indukované   epidemiologie   MeSH
• nemoci z povolání * chemicky indukované   epidemiologie   MeSH
• oxid křemičitý toxicita   MeSH
• pracovní expozice * škodlivé účinky   analýza   MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azbest MeSH
• karcinogeny * MeSH
• oxid křemičitý MeSH

Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. AA initially was involved in the outbreak of cases of rapidly progressive renal fibrosis reported in Belgium after intake of root extracts of Aristolochia fangchi imported from China. A high prevalence of UTUC was found in these patients. The common molecular link between Balkan and Belgian nephropathy cases was the detection of aristolactam-DNA adducts in renal tissue and UTUC. These adducts are not only biomarkers of prior exposure to AA, but they also trigger urothelial malignancy by inducing specific mutations (A:T to T:A transversion) in critical genes of carcinogenesis, including the tumor-suppressor TP53. Such mutational signatures are found in other cases worldwide, particularly in Taiwan, highlighting the general public health issue of AA exposure by traditional phytotherapies.

• Klíčová slova
• Aristolochia species, Balkan endemic nephropathy, aristolochic acid, aristolochic acid nephropathy, upper tract urothelial carcinoma,
• MeSH
• adukty DNA MeSH
• Aristolochia MeSH
• balkánská nefropatie chemicky indukované   diagnóza   patologie   terapie   MeSH
• karcinogeny toxicita   MeSH
• karcinom z přechodných buněk chemicky indukované   MeSH
• kyseliny aristolochové toxicita   MeSH
• lidé MeSH
• nádory ledvin chemicky indukované   MeSH
• nádory močovodu chemicky indukované   MeSH
• plošný screening MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adukty DNA MeSH
• aristolochic acid I MeSH Prohlížeč
• karcinogeny MeSH
• kyseliny aristolochové MeSH