The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles

Our plain-English summary of The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles, by K. Donaldson, P.J. Borm, V. Castranova, et al (Particle and Fibre Toxicology, 2009).

The study

• Authors: K. Donaldson, P.J. Borm, V. Castranova, M. Gulumian
• Journal: Particle and Fibre Toxicology
• Published: 2009;6:13
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In vitro studies with particles are a major staple of particle toxicology, generally used to investigate mechanisms and better understand the molecular events underlying cellular effects. However, there is ethical and financial pressure in nanotoxicology, the new sub-specialty of particle toxicology, to avoid using animals. Therefore an increasing amount of studies are being published using in vitro approaches and such studies require careful interpretation. We point out here that 3 different conventional pathogenic particle types, PM10, asbestos and quartz, which cause diverse pathological effects, have been reported to cause very similar oxidative stress effects in cells in culture. We discuss the likely explanation and implications of this apparent paradox, and its relevance for testing in nanotoxicology.

In plain English

This article was a review, not a new experiment. The authors compared three kinds of particles that deposit in the lung: asbestos, quartz and PM10 (particles in polluted air). They looked at the diseases each is associated with and at published studies of their effects on cells grown in the laboratory. They described what they called an apparent paradox. Numerous cell studies indicated that the three particle types have similar activities in cells, mostly based around oxidative stress, yet the particles cause different diseases. In the authors' account, mesothelioma is virtually unique to asbestos exposure, and only asbestos causes pleural plaques. They also pointed to other examples, glass fibres, kaolin and purified single-walled carbon nanotubes, where cell testing has been shown to misclassify health hazard. The authors concluded that a particle that causes oxidative stress in cultured cells could, in theory, behave like quartz, asbestos or PM10, and the cell data would not show which. They said great care is needed in interpreting such data when testing nanoparticles. They argued that animal studies and studies of how particles move through the body remain needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review
• Who was studied: No study population. The review considered three particle types (asbestos, quartz and PM10), the diseases associated with them, and published in vitro (cell culture) studies of their effects.
• Exposure: Asbestos (no fibre type specified in the main text), quartz, and PM10 (ambient particulate air pollution), compared for their effects on cells in culture and the diseases associated with them. The article's wider focus is the testing of nanoparticles.
• Main results:
  • According to the reviewed in vitro studies, asbestos, quartz and PM10 have similar activities in cells in culture, including oxidative stress, NF-κB activation, pro-inflammatory effects and oxidative adduct formation.
  • The three particle types cause different types of disease even though they deposit in the same target tissue, the airspaces of the lung.
  • The authors stated that mesothelioma (of the pleura or peritoneum) is virtually unique to asbestos exposure and is not caused by the other particles discussed.
  • The authors stated that, of the three particle types, only asbestos causes pleural plaques.
  • The authors cited glass fibres and kaolin as false positives in cell tests, and purified single-walled carbon nanotubes as a false negative.
  • The authors stated that the toxicokinetic work available suggests larger particles do not, on the whole, translocate (move away from the lung) to any appreciable degree, except for asbestos.
• The authors' conclusion: The authors concluded that great care should be taken in interpreting in vitro data. In their view, a particle that causes oxidative stress in cultured cells could, in theory, behave like quartz, asbestos or PM10, and the in vitro data would not show which. They argued that toxicokinetics and in vivo testing of nanoparticles remain needed.

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress.

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