Nejvíce citovaný článek - PubMed ID 26106142
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
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.
- Klíčová slova
- Air pollution, Carcinogenesis, Diesel exhaust, Genotoxicity, Inflammation, Occupational exposure, Smoking, Tumor metastasis, Tumor microenvironment, Tumor promotion,
- MeSH
- látky znečišťující vzduch * toxicita MeSH
- lidé MeSH
- monitorování životního prostředí MeSH
- nádorové mikroprostředí MeSH
- nádory plic * chemicky indukované genetika MeSH
- pevné částice toxicita MeSH
- polycyklické aromatické uhlovodíky * toxicita MeSH
- receptory aromatických uhlovodíků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- látky znečišťující vzduch * MeSH
- pevné částice MeSH
- polycyklické aromatické uhlovodíky * MeSH
- receptory aromatických uhlovodíků MeSH
BACKGROUND: Food contact articles (FCAs) are manufactured from food contact materials (FCMs) that include plastics, paper, metal, glass, and printing inks. Chemicals can migrate from FCAs into food during storage, processing, and transportation. Food contact materials' safety is evaluated using chemical risk assessment (RA). Several challenges to the RA of FCAs exist. OBJECTIVES: We review regulatory requirements for RA of FCMs in the United States and Europe, identify gaps in RA, and highlight opportunities for improving the protection of public health. We intend to initiate a discussion in the wider scientific community to enhance the safety of food contact articles. DISCUSSION: Based on our evaluation of the evidence, we conclude that current regulations are insufficient for addressing chemical exposures from FCAs. RA currently focuses on monomers and additives used in the manufacture of products, but it does not cover all substances formed in the production processes. Several factors hamper effective RA for many FCMs, including a lack of information on chemical identity, inadequate assessment of hazardous properties, and missing exposure data. Companies make decisions about the safety of some food contact chemicals (FCCs) without review by public authorities. Some chemical migration limits cannot be enforced because analytical standards are unavailable. CONCLUSION: We think that exposures to hazardous substances migrating from FCAs require more attention. We recommend a) limiting the number and types of chemicals authorized for manufacture and b) developing novel approaches for assessing the safety of chemicals in FCAs, including unidentified chemicals that form during or after production. https://doi.org/10.1289/EHP644.
- MeSH
- bezpečnost potravin metody MeSH
- hodnocení rizik MeSH
- kontaminace potravin analýza statistika a číselné údaje MeSH
- lidé MeSH
- nebezpečné látky analýza MeSH
- obaly potravin * MeSH
- plastické hmoty MeSH
- veřejné zdravotnictví MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
- Názvy látek
- nebezpečné látky MeSH
- plastické hmoty MeSH