Chronic Respiratory Toxicity

Prolonged exposure of lung tissue to materials, inhaled or otherwise, may challenge the tissue leading to cell death or loss of viability over time. Other changes due to long term exposure or prolonged tissue challenge can manifest in a variety of key events and markers of disease. IIVS’s Respiratory Toxicology Program offers several pulmonary models that will allow the assessment of long term exposure and effects, with cultures that can be maintained for weeks or months.

While assays used for acute toxicity (cytotoxicity and viability) apply for prolonged exposure/culture assessment, additional assays that highlight markers of chronic toxicity may be chosen.

Tissue Marker Content

Many long term effects include the appearance or upregulation of markers associated with certain disease states. Tissue lysates can be assayed to quantify markers of interest (e.g. collagen, a marker of fibrosis). While tissue markers may change in an acute manner, chronic effects may be more pronounced following long-term buildup of markers.

Histological Assessment

Pulmonary tissues undergo distinct changes upon loss of viability, cytotoxic, and long-term adverse events. The Histological assessment of long term changes such as tissue remodeling, collagen deposition, and the presence of increased numbers of activated macrophages can be a powerful tool in deciphering the effects of test materials over time. The evaluation of stained tissues is available, with focused, stain- and tissue-specific determinations possible.

Talk to IIVS about your custom evaluation needs!  We can work with you if you have specific biochemical or histological cytotoxicity and viability markers in mind!

PCLS at day 16 treated with 0.1 mU/mL bleomycin showing broad strands and a tangled mass of collagen fibers. Section with Masson’s trichrome stain)
PCLS treated with 1 μM carmustine at day 28. The bronchiole shows a loss of lining epithelium. Some of the surrounding alveoli also show degeneration. Section H&E stained.
PCLS at Day 8 following exposure to 10 mU/mL bleomycin. Section immunostained with ED-1 macrophage marker showing clumps and of activated macrophages filling the alveolar spaces.