Lung Carcinogen Research Articles

Bias analysis on socioeconomic status and lung cancer in a pooled international case-control study

Abstract Background Low socioeconomic status (SES) groups showed increased lung cancer risks even after adjustment for smoking habits and other exposures to lung carcinogens. Although several biases were often indicated and discussed, only few studies quantified the impact of potential biases. Methods We conducted a bias analysis on the association of lung cancer and SES using data from the SYNERGY project, including 12 case-control studies with 18 study centres from Europe and Canada (16,550 cases, 20,147 controls). SES in quartiles was derived from the International Socio-Economic Index of occupational status (ISEI). Odds ratios (OR) with 95% confidence intervals (CI) were estimated by logistic regression adjusting for age, study centre, and smoking. In addition, we estimated natural direct SES effects and natural indirect smoking effects by inverse odds ratio weighting. In a multiple quantitative bias analysis, we considered impacts of misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by a protective genetic factor, and created 95% simulation intervals (SI) by bootstrap. All analyses were stratified by sex. Results Adjustment for smoking as well as natural effects estimation showed that nearly half of lung cancer risks of lower SES groups in men and up to one third in women were attributable to smoking. Consideration of all types of bias reduced lung-cancer risks in the fully adjusted logistic regression models, with the strongest impact by selection bias: For the 4th versus 1st (highest) ISEI quartile OR decreased from 1.83 (1.69-1.98 CI) to 1.50 (1.30-1.73 SI) in men, and OR 1.48 (1.27-1.72 CI) to 1.20 (0.96-1.53 SI) in women. Conclusions Smoking is the main target for prevention of lung cancer, along with occupational and environmental exposures, in particular in lower SES groups. This finding remains, though our analysis revealed reduced lung-cancer risks of lower SES groups after multiple bias adjustment. Key messages • Impact of potential biases was quantified in the association of SES and lung cancer. • Lung cancer risks were partially attributable to smoking and multiple biases.

Occupational exposure to nickel or hexavalent chromium and the risk of lung cancer (SYNERGY)

Abstract Background Hexavalent chromium (Cr(VI)) and nickel (Ni) are known occupational carcinogens, with frequent exposures, for example, in welding-related activities. However, limited evidence exists on the exposure-response relationship of Cr(VI) or Ni with lung-cancer risk. We estimated lung-cancer risks based on quantitative indices of occupational exposure to each metal, and their interaction with smoking habits. Methods Fourteen case-control studies from Europe and Canada (16,901 cases, 20,965 control subjects) were pooled. A measurement-based job-exposure matrix was used to estimate year- and region-specific exposure levels for Cr(VI) and Ni, which were linked to the study subjects’ occupational histories. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for study, age group, smoking, and exposure to other occupational lung carcinogens. Results The OR for the highest quartile (>99.5 μg/m3-years) of cumulative exposure to Cr(VI) in men was 1.32 (95% CI 1.19-1.47) and for nickel (highest quartile >78.1 μg/m3-years) OR = 1.29 (95% CI 1.15-1.45). Corresponding effect estimates in women were slightly lower. The joint effects of Cr(VI) and nickel with smoking were generally greater than additive. Conclusions We observed positive exposure-response relationships in the low-dose range of Cr(VI) and Ni exposures, based on a large study population including detailed information on smoking habits and a measurement-based job-exposure matrix. Although, we cannot rule out a combined classical measurement and Berkson error structure that may have caused bias in our risk estimates, our results provide empirical evidence to further specify preventive measures at the workplace in order to protect workers from hazardous substances. Key messages • Relatively low cumulative levels of occupational exposure to Cr(VI) and Ni were associated with increased ORs for lung cancer, particularly in men. • Important empirical insights for the prevention of cancer at the workplace can be drawn from the results.

One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

Fullerene and fullerene whisker are not carcinogenic to the lungs and pleura in rat long-term study after 2-week intra-tracheal intrapulmonary administration

Fullerene whiskers (FLW)s are thin rod-like structures composed of C60 and C70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity.

Unintended Consequences of Urban Expansion and Gold Mining: Elevated Indoor Radon Levels in Gauteng Communities’ Neighboring Gold Mine Tailings

The province of Gauteng in South Africa has a rich history of gold mining, which has driven economic growth and urbanization. Gold mining has also created over 270 gold mine tailings (GMT), now surrounded by human settlements due to a housing shortage. These GMT pose a health risk as they harbor elevated uranium, which over time undergoes radioactive decay to produce radon, a known lung carcinogen. This study aimed to investigate the potential correlation between the proximity to gold mine tailings (GMT) and indoor radon concentrations in Gauteng’s residential dwellings. Volume activity of radon (VAR) inside 330 residential dwellings was measured in residential dwellings located proximally (<2 km) and distally (>2 km) to gold mine tailings using AlphaE radon monitors during winter. An interviewer-administered questionnaire was utilized to obtain data on factors that may influence indoor radon activities. Descriptive statistics and bivariate logistic regression analyzed the influence of proximity to gold mine tailings and dwelling characteristics on VAR. Furthermore, VAR was compared to the World Health Organization (WHO) radon reference level of 100 Bq/m3. Residential dwellings near gold mine tailings had significantly higher average indoor radon concentrations (103.30 Bq/m3) compared to the control group (65.19 Bq/m3). Residential dwellings proximal to gold mine tailings were three times more likely to have VAR beyond the WHO reference level of 100 Bq/m3. Furthermore, they had estimated annual effective doses of 2.60 mSv/y compared to 1.64 mSv/y for the control group. This study highlighted a concerning association between proximity to gold mine tailings and elevated indoor radon levels. Public health interventions prioritizing residential dwellings near gold mine tailings are crucial. Educational campaigns and financial assistance for radon mitigation systems in high-risk dwellings are recommended. Residents near gold mine tailings are encouraged to ensure continuous natural ventilation through frequent opening of windows and doors.

Acute particulate hexavalent chromium exposure induces DNA double-strand breaks and activates homologous recombination repair in rat lung tissue.

Hexavalent chromium [Cr(VI)] is an established human lung carcinogen, but the carcinogenesis mechanism is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driver of Cr(VI)-induced lung cancer. Unrepaired DNA double-strand breaks are the underlying cause, and homologous recombination repair is the primary mechanism preventing Cr(VI)-induced DNA breaks from causing chromosome instability. Cell culture studies show acute Cr(VI) exposure causes DNA double-strand breaks and increases homologous recombination repair activity. However, the ability of Cr(VI)-induced DNA breaks and repair impact has only been reported in cell culture studies. Therefore, we investigated whether acute Cr(VI) exposure could induce breaks and homologous recombination repair in rat lungs. Male and female Wistar rats were acutely exposed to either zinc chromate particles in a saline solution or saline alone by oropharyngeal aspiration. This exposure route resulted in increased Cr levels in each lobe of the lung. We found Cr(VI) induced DNA double-strand breaks in a concentration-dependent manner, with females being more susceptible than males, and induced homologous recombination repair at similar levels in both sexes. Thus, these data show this driving mechanism discovered in cell culture indeed translates to lung tissue in vivo.

Thorium Alters Lung Surfactant Protein Expression in Alveolar Epithelial Cells: In Vitro and In Vivo Investigation.

Thorium-232 (Th), the most abundant naturally occurring nuclear fuel, has been identified as a sustainable source of energy. In view of its large-scale utilization and human evidence of lung disorders and carcinogenicity, it is imperative to understand the effect of Th exposure on lung cells. The present study investigated the effect of Th-dioxide (1-100 μg/mL, 24-48 h) on expression of surfactant proteins (SPs) (SP-A, SP-B, SP-C, and SP-D, which are essential to maintain lung's surface tension and host-defense) in human lung cells (WI26 and A549), representative of alveolar cell type-I and type-II, respectively. Results demonstrated the inhibitory effect of Th on transcriptional expression of SP-A, SP-B, and SP-C. However, Th promoted the mRNA expression of SP-D in A549 and reduced its expression in WI26. To a significant extent, the effect of Th on SPs was found to be in accordance with their protein levels. Moreover, Th exposure altered the extracellular release of SP-D/A from A549, which remained unaltered in WI26. Our results suggested the differential role of oxidative stress and ATM and HSP90 signaling in Th-induced alterations of SPs. These effects of Th were found to be consistent in lung tissues of mice exposed to Th aerosols, suggesting a potential role of SPs in Th-associated lung disorders.

LncRNA XIST modulates miR-328-3p ectopic expression in lung injury induced by tobacco-specific lung carcinogen NNK both in vitro and in vivo.

It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice. LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice. Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo.

Prolonged Particulate Hexavalent Chromium Exposure Induces DNA Double-Strand Breaks and Inhibits Homologous Recombination Repair in Primary Rodent Lung Cells.

Hexavalent chromium [Cr(VI)] is a known lung carcinogen and a driving mechanism in human lung cells for Cr(VI)-induced lung cancer is chromosome instability, caused by prolonged Cr(VI) exposure inducing DNA double-strand breaks, while simultaneously inhibiting the repair of these breaks. In North Atlantic right whales, Cr(VI) induces breaks but does not inhibit repair. It is unclear if this repair inhibition is specific to human lung cells or occurs in other species, as it has only been considered in humans and North Atlantic right whales. We evaluated these outcomes in rodent cells, as rodents are an experimental model for metal-induced lung carcinogenesis. We used a guinea pig lung fibroblast cell line, JH4 Clone 1, and rat lung fibroblasts. Cells were exposed to two different particulate Cr(VI) compounds, ranging from 0 to 0.5 ug/cm2, for 24 or 120h and assessed for cytotoxicity, DNA double-strand breaks, and DNA double-strand break repair. Both particulate Cr(VI) compounds induced a concentration-dependent increase in cytotoxicity and DNA double-strand breaks after acute and prolonged exposures. Notably, while the repair of Cr(VI)-induced DNA double-strand breaks increased after acute exposure, the repair of these breaks was inhibited after prolonged exposure. These results are consistent with outcomes in human lung cells indicating rodent cells respond like human cells, while whale cells have a markedly different response.

Transcriptomic analysis reveals particulate hexavalent chromium regulates key inflammatory pathways in human lung fibroblasts as a possible mechanism of carcinogenesis

Hexavalent chromium [Cr(VI)] is considered a major environmental health concern and lung carcinogen. However, the exact mechanism by which Cr(VI) causes lung cancer in humans remains unclear. Since several reports have demonstrated a role for inflammation in Cr(VI) toxicity, the present study aimed to apply transcriptomics to examine the global mRNA expression in human lung fibroblasts after acute (24 h) or prolonged (72 and 120 h) exposure to 0.1, 0.2 and 0.3 μg/cm2 zinc chromate, with a particular emphasis on inflammatory pathways. The results showed Cr(VI) affected the expression of multiple genes and these effects varied according to Cr(VI) concentration and exposure time. Bioinformatic analysis of RNA-Seq data based on the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaCore databases revealed multiple inflammatory pathways were affected by Cr(VI) treatment. qRT-PCR data corroborated RNA-Seq findings. This study showed for the first time that Cr(VI) regulates key inflammatory pathways in human lung fibroblasts, providing novel insights into the mechanisms by which Cr(VI) causes lung cancer.

Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium.

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption of Cd involves transporters for essential metals, notably iron and zinc. These transporters determine the Cd body burden because only a minuscule amount of Cd can be excreted each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen, but the current evidence suggests that the effects of Cd on cancer risk extend beyond the lung. A two-year bioassay demonstrated that Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cells transformed to malignant cells when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it influences gene expression through interactions with essential metals and various proteins. The present review highlights the epidemiological studies that connect an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is given to the impact of body iron stores on the absorption of Cd, and its implications for breast cancer prevention in highly susceptible groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer cell transformation, under in vitro conditions, are briefly discussed. The potential role for the ZnT1 efflux transporter in the cellular acquisition of tolerance to Cd cytotoxicity is highlighted.

DNMT3a-mediated upregulation of the stress inducible protein sestrin-2 contributes to malignant transformation of human bronchial epithelial cells following nickel exposure

BackgroundNickel is a confirmed human lung carcinogen. Nonetheless, the molecular mechanisms driving its carcinogenic impact on lung tissue remain poorly defined. In this study, we assessed SESN2 expression and the signaling pathways responsible for cellular transformation in human bronchial epithelial cells (HBECs) as a result of nickel exposure. MethodsWe employed the Western blotting to determine the induction of SESN2 by nickel. To clarify the signaling pathways leading to cellular transformation following nickel exposure, we applied techniques such as gene knockdown, methylation-specific PCR, and chromatin immunoprecipitation. ResultExposure to nickel results in the upregulation of SESN2 and the initiation of autophagy in human bronchial epithelial cells (HBECs). This leads to degradation of HUR protein and consequently downregulation of USP28 mRNA, PP2AC protein, β-catenin protein, and diminished VHL transcription, culminating in the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the malignant transformation of these cells. Mechanistic studies revealed that the increased expression of SESN2 is attributed to the demethylation of the SESN2 promoter induced by nickel, a process facilitated by decreased DNA methyl-transferase 3 A (DNMT3a) expression, while The downregulation of VHL transcription is linked to the suppression of the PP2A-C/GSK3β/β-Catenin/C-Myc pathway. Additionally, we discovered that SESN2-mediated autophagy triggers the degradation of HUR protein, which subsequently reduces the stability of USP28 mRNA and inhibits the PP2A-C/GSK3β/β-Catenin pathway and c-Myc transcription in HBECs post nickel exposure. ConclusionOur results reveal that nickel exposure leads to the downregulation of DNMT3a, resulting in the hypomethylation of the SESN2 promoter and its protein induction. This triggers autophagy-dependent suppression of the HUR/USP28/PP2A/β-Catenin/c-Myc pathway, subsequently leading to reduced VHL transcription, accumulation of HIF-1α protein, and the malignant transformation of human bronchial epithelial cells (HBECs). Our research offers novel insights into the molecular mechanisms that underlie the lung carcinogenic effects of nickel exposure. Specifically, nickel induces aberrant DNA methylation in the SESN2 promoter region through the decrease of DNMT3a levels, which ultimately leads to HIF-1α protein accumulation and the malignant transformation of HBECs. Specifically, nickel initiates DNA-methylation of the SESN2 promoter region by decreasing DNMT3a, ultimately resulting in HIF-1α protein accumulation and malignant transformation of HBECs. This study highlights DNMT3a as a potential prognostic biomarker or therapeutic target to improve clinical outcomes in lung cancer patients.

Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

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. 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. 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). 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; = 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). 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.

Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats.

To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.

Benzene exposure and risk of lung cancer in the Norwegian Offshore Petroleum Worker cohort: a prospective case-cohort study

ObjectiveThe objective of our study was to examine whether occupational exposure to benzene is associated with lung cancer among males in the Norwegian Offshore Petroleum Workers cohort.MethodsAmong 25 347 male...

Hexavalent Chromium Targets Securin to Drive Numerical Chromosome Instability in Human Lung Cells.

Hexavalent chromium [Cr(VI)] is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass. A key regulator of these events is securin, which acts by regulating the cleavage ability of separase. Thus, in this study we investigated securin disruption by Cr(VI) exposure. We exposed human lung cells to a particulate Cr(VI) compound, zinc chromate, for acute (24 h) and prolonged (120 h) time points. We found prolonged Cr(VI) exposure caused marked decrease in securin levels and function. After prolonged exposure at the highest concentration, securin protein levels were decreased to 15.3% of control cells, while securin mRNA quantification was 7.9% relative to control cells. Additionally, loss of securin function led to increased separase activity manifested as enhanced cleavage of separase substrates; separase, kendrin, and SCC1. These data show securin is targeted by prolonged Cr(VI) exposure in human lung cells. Thus, a new mechanistic model for Cr(VI)-induced carcinogenesis emerges with centrosome and centromere disruption as key components of numerical chromosome instability, a key driver in Cr(VI) carcinogenesis.

Patterns in medical surveillance of workers exposed to lung carcinogens

Abstract One of the most common causes of lung cancer is exposure to occupational carcinogens. Free silica, diesel exhaust fumes, dyes, radon and with asbestos at the top of the list, differ by percentage according to the predominant professional activities in each country. The occupational health doctor is directly involved in the surveillance of the exposed worker, during work or post exposure, in the diagnosis and reporting of occupational cancers. Efficient screening followed by reporting and monitoring cases of occupational lung cancer and, last but not least, reintegration into professional activity are important steps in the medical surveillance of the worker exposed to occupational lung carcinogens. Standardised information collected at the level of occupational exposure monitoring systems, separated by carcinogen category and profession, may form the basis of control and prevention plans. Harmonising medical surveillance at European and global level can lead to a decrease in the incidence and mortality of work-related lung cancer.

Using particle dimensionality-based modeling to estimate lung carcinogenicity of 3D printer emissions.

The use of 3D printing technologies by industry and consumers is expanding. However, the approaches to assess the risk of lung carcinogenesis from the emissions of 3D printers have not yet been developed. The objective of the study was to demonstrate a methodology for modeling lung cancer risk related to specific exposure levels as derived from an experimental study of 3D printer emissions for various types of filaments (ABS, PLA, and PETG). The emissions of 15 filaments were assessed at varying extrusion temperatures for a total of 23 conditions in a Class 1,000 cleanroom following procedures described by ANSI/CAN/UL 2904. Three approaches were utilized for cancer risk estimation: (a) calculation based on PM2.5 and PM10 concentrations, (b) a proximity assessment based on the pulmonary deposition fraction, and (c) modeling based on the mass-weighted aerodynamic diameter of particles. The combined distribution of emitted particles had the mass median aerodynamic diameter (MMAD) of 0.35 μm, GSD 2.25. The average concentration of PM2.5 was 25.21 μg/m3 . The spline-based function of aerodynamic diameter allowed us to reconstruct the carcinogenic potential of seven types of fine and ultrafine particles (crystalline silica, fine TiO2 , ultrafine TiO2 , ambient PM2.5 and PM10, diesel particulates, and carbon nanotubes) with a correlation of 0.999, P < 0.00001. The central tendency estimation of lung cancer risk for 3D printer emissions was found at the level of 14.74 cases per 10,000 workers in a typical exposure scenario (average cumulative exposure of 0.3 mg/m3 - years), with the lowest risks for PLA filaments, and the highest for PETG type.

Risk assessment for conventional diesel exhaust (before 1990) and lung cancer in a cohort of miners.

Diesel exhaust in the latter half of the 20th century has been found to be a lung carcinogen. Conventional diesel emissions continue in the transportation, mining, construction, and farming industries. From the Diesel Exhaust in Miners Study, a public-use dataset was used to calculate the excess lifetime risk of lung cancer associated with diesel exposure (1947-1997). Excess rates of lung cancer mortality associated with respirable elemental carbon (REC) and possible other mining exposures (e.g., oil mists, explosives emissions) were investigated using Poisson regression methods. Lung cancer mortality declined with increasing employment duration while increasing with cumulative REC and non-diesel exposures, suggesting a strong worker survivor effect. Attenuation of the REC effect was observed with increasing cumulative exposure. After adjustment for employment duration, the excess rate ratio for lung cancer mortality was 0.67 (95% CI=0.35-0.99) for a 10-year lagged exposure to 200μg/m3 REC, a typical below-ground exposure in the study mines. At exposures of 200, 10, and 1μg/m3 REC, the estimated excess lifetime risks, respectively, were 119, 43, and 8.7 per thousand. Analysis of an inception cohort hired after dieselization commenced produced smaller and less certain estimates of lifetime risk. From exposures to conventional diesel engine exhaust common in occupational groups in the past, the excess lifetime risk of lung cancer was more than 5%. Ambient REC exposures in the general population were estimated to confer lifetime risks of 0.14 to 14 per thousand, depending on assumptions made.