Multi-Walled Carbon Nanotubes Accelerate Leukaemia Development in a Mouse Model

Area of Science:

• Environmental Health
• Toxicology
• Oncology

Background:

• Inflammation is a known risk factor for various cancers, including hematologic malignancies like myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML).
• Multi-walled carbon nanotubes (MWCNTs) are increasingly utilized in research and industry, leading to heightened human exposure.
• Assessing the health risks associated with MWCNTs, particularly their impact on cancer development and progression, is critical.

Purpose of the Study:

• To investigate the effect of MWCNTs exposure on the progression of virus-induced leukemia in a murine model.
• To examine the role of inflammation and reactive oxygen species (ROS) in MWCNTs-induced cancer acceleration.
• To evaluate the potential protective effects of immunodeficiency and PEG-modified MWCNTs.

Main Methods:

• Mice were exposed to MWCNTs to assess the impact on spontaneous leukemia progression.
• Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and ROS levels were measured in response to MWCNTs exposure.
• Experiments were conducted using immunodeficient mice and mice treated with PEG-modified MWCNTs to evaluate mitigation strategies.

Main Results:

• MWCNTs exposure significantly accelerated the progression of MOL4070LTR virus-induced leukemia in mice.
• Exposure to MWCNTs led to elevated levels of pro-inflammatory cytokines and induced ROS in a murine macrophage cell line.
• These pro-inflammatory effects and leukemia acceleration were notably reduced in immunodeficient mice and when using PEG-modified MWCNTs.

Conclusions:

• MWCNTs exposure can exacerbate leukemia progression, likely through inflammatory pathways and ROS induction.
• Immunodeficiency and surface modification of MWCNTs (e.g., PEGylation) may mitigate these adverse effects.
• The findings highlight the importance of rigorous safety assessments for MWCNTs, particularly concerning individuals with or at risk for hematologic cancers.