How does tar affect mice? - briefly
Tar exposure induces respiratory irritation, weight loss, and heightened mortality in laboratory mice, while also provoking inflammatory responses and DNA damage in lung tissue.
How does tar affect mice? - in detail
Tar exposure in laboratory rodents produces measurable physiological and pathological changes that are widely used to model human tobacco‑related disease. Inhalation of aerosolized tar, dermal application of condensed tar, or oral gavage of tar extracts deliver polycyclic aromatic hydrocarbons (PAHs), nicotine, phenols, and heavy metals to the animal’s system. These constituents interact with cellular receptors, generate reactive oxygen species, and form DNA adducts, leading to a cascade of effects.
Respiratory tract:
- Ciliary dysfunction and epithelial desquamation reduce mucociliary clearance.
- Inflammatory infiltrates of neutrophils and macrophages appear within hours, followed by chronic bronchitis‑like changes.
- Pulmonary fibrosis develops after repeated exposure, evidenced by collagen deposition and reduced lung compliance.
Cardiovascular system:
- Endothelial nitric‑oxide synthase activity declines, impairing vasodilation.
- Platelet aggregation increases, raising thrombosis risk.
- Histopathology shows arterial wall thickening and atherosclerotic plaque formation in high‑dose groups.
Carcinogenesis:
- DNA adducts from benzo[a]pyrene and related PAHs induce mutations in the p53 and KRAS genes.
- Tumor incidence rises in lung, oral cavity, and skin tissues, with latency inversely proportional to dose.
- Tumor multiplicity correlates with cumulative exposure measured in mg/kg of tar.
Metabolic and systemic effects:
- Liver enzymes (CYP1A1, CYP1B1) are up‑regulated, indicating enhanced xenobiotic metabolism.
- Serum cortisol and catecholamine levels increase, reflecting stress‑axis activation.
- Weight loss and reduced feed efficiency occur in animals receiving high concentrations of tar aerosol.
Behavioral outcomes:
- Open‑field testing shows decreased locomotor activity and increased anxiety‑like behavior.
- Conditioned place preference assays reveal reinforcing properties of nicotine within tar, influencing addiction‑related pathways.
Dose‑response relationships:
- Low‑level exposure (0.1 mg/m³) produces transient inflammatory markers without lasting tissue damage.
- Moderate exposure (0.5 mg/m³) leads to chronic bronchitis and early vascular changes.
- High exposure (≥1.0 mg/m³) results in pronounced fibrosis, atherosclerosis, and tumor formation within 6–12 months.
Experimental considerations:
- Species differences affect susceptibility; C57BL/6 mice display greater pulmonary inflammation than BALB/c strains.
- Exposure duration (continuous vs. intermittent) modifies the severity of outcomes.
- Control groups receiving vehicle without tar are essential for attributing observed effects to tar constituents.
Overall, tar administration in mice produces a spectrum of toxicological endpoints that mirror human health risks associated with tobacco smoke, providing a robust platform for evaluating preventive and therapeutic interventions.