AIM: To investigate the effect of acute (daily) inhalation of nanoparticles (NPs) on the transcriptomic profile of male nanocomposite research workers with a history of long-term exposure (years). MATERIALS & METHODS: Whole genome mRNA and miRNA expression changes were analyzed from blood samples collected before and after machining or welding. Exposure in the work environment was assessed using stationary and personal monitoring. RESULTS: Following PM0.1 exposure, a significant decrease in the expression of DDIT4 and FKBP5, genes involved in the stress response, was detected in exposed workers. In the Machining group, the DDIT4 expression correlated with the exposure dose. Increased levels of miR30-d-5p and miR-3613-5p (both involved in carcinogenesis) in welders were associated with the NP exposure dose, highlighting their potential suitability as inhalation exposure markers. CONCLUSION: The results from this pilot transcriptomic analysis (mRNA and miRNA) indicate that exposure to NPs contributes to immune system deregulation and alters the pathways related to cancer. Therefore, the use of protective equipment, as well as obtaining more data by additional research, is highly recommended.

This is a follow-up study to our previous research that examined the acute effects of occupational inhalation exposure to nanoparticles (NPs) in females without a previous exposure history. This time, we reexamined the impacts of acute exposure in a group of 18 male workers, including welders and nanocomposite machinists with a long-term previous exposure history at the transcriptomic level. Whole genome transcriptomics studies the complete set of RNA molecules, or transcripts, produced in a cell or organism at a specific time. The analysis allows us to understand which genes are active/inactive, how they are regulated, and how they contribute to various biological processes or diseases. We looked at changes in mRNA and miRNA (types of RNA) from blood samples taken before and after workers were exposed to dust and fumes during machining and welding. We also monitored the exposure doses. The results suggest that inhaled NPs may present an occupational hazard to human health. The transcriptomic analysis shows that exposure to welding fumes and nanocomposite dust from machining affects the immune system and alters cancer-related pathways. Our research helps to understand NP exposure effects and may contribute to minimizing the negative health consequences of their inhalation.

• Keywords
• Occupational exposure, machining, nanoparticles, transcriptome changes, welding,
• MeSH
• Adult MeSH
• Inhalation Exposure adverse effects   analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger genetics   blood   MeSH
• MicroRNAs genetics   blood   MeSH
• Nanoparticles * adverse effects   MeSH
• Occupational Exposure * adverse effects   analysis   MeSH
• Gene Expression Profiling MeSH
• Transcriptome * drug effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Messenger MeSH
• MicroRNAs MeSH

Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% of all lung cancer deaths. Increased risk associated with living near trafficked roads, occupational exposure to diesel exhaust, indoor coal combustion and cigarette smoking, suggest that combustion components in ambient fine particulate matter (PM2.5), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers of lung cancer. Activation of the aryl hydrocarbon receptor (AhR) induces expression of xenobiotic-metabolizing enzymes (XMEs) and increase PAH metabolism, formation of reactive metabolites, oxidative stress, DNA damage and mutagenesis. Lung cancer tissues from smokers and workers exposed to high combustion PM levels contain mutagenic signatures derived from PAHs. However, recent findings suggest that ambient air PM2.5 exposure primarily induces lung cancer development through tumor promotion of cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss the role of AhR and PAHs in lung cancer development caused by air pollution focusing on the tumor promoting properties including metabolism, immune system, cell proliferation and survival, tumor microenvironment, cell-to-cell communication, tumor growth and metastasis. We suggest that the dichotomy in lung cancer patterns observed between smoking and outdoor air PM2.5 represent the two ends of a dose-response continuum of combustion PM exposure, where tumor promotion in the peripheral lung appears to be the driving factor at the relatively low-dose exposures from ambient air PM2.5, whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.

• Keywords
• Air pollution, Carcinogenesis, Diesel exhaust, Genotoxicity, Inflammation, Occupational exposure, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion,
• MeSH
• Air Pollutants * toxicity   MeSH
• Humans MeSH
• Environmental Monitoring MeSH
• Tumor Microenvironment MeSH
• Lung Neoplasms * chemically induced   genetics   MeSH
• Particulate Matter toxicity   MeSH
• Polycyclic Aromatic Hydrocarbons * toxicity   MeSH
• Receptors, Aryl Hydrocarbon genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• Air Pollutants * MeSH
• Particulate Matter MeSH
• Polycyclic Aromatic Hydrocarbons * MeSH
• Receptors, Aryl Hydrocarbon MeSH