Toxicology and Applied Pharmacology 2004-11-15

Increased vulnerability of neonatal rats and mice to 1-nitronaphthalene-induced pulmonary injury.

Michelle V Fanucchi, Kimberly C Day, Candice C Clay, Charles G Plopper

Index: Toxicol. Appl. Pharmacol. 201(1) , 53-65, (2004)

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Abstract

The postnatal period of lung development is a critical window of susceptibility to environmental toxicants, including polyaromatic hydrocarbons (PAHs) and furans. To determine whether the increased susceptibility of neonatal lung injury due to environmental toxicants is a universal response across species and also applies to nitrated compounds, adult and 7-day-old male mice and rats were given a single intraperitoneal dose (0, 12.5, 25, 50, or 100 mg/kg) of 1-nitronaphthalene and killed 24 h later. Exposure to 1-nitronaphthalene, a nitro-polyaromatic hydrocarbon, results in pulmonary lesions in both adult rats and mice, although the severity of the injury is species-specific (greater in rats than in mice). Pulmonary lesions, as assessed by quantitative histopathology, included dose-dependent vacuolization and exfoliation of both ciliated and nonciliated airway epithelial cells throughout the airway tree in both rats and mice. In both species, the 7-day-old animals were more susceptible to injury by 1-nitronaphthalene than adult animals. In contrast to adult response, neonatal mice were more susceptible to 1-nitronaphthalene-induced pulmonary injury than neonatal rats. This indicates that neonatal susceptibility to environmental pollutant-induced lung injury cannot be reliably predicted based on adult susceptibility.