Cigarette smoke vapor-phase effects in the rat upper respiratory tract

The temporal and regional cytotoxic and proliferative potential of whole smoke or the vapor phase of smoke from reference cigarettes was investigated. Male F344 rats were exposed nose-only 1 h/day for up to 20 weekdays to 500 mg/m(3) whole smoke, the vapor-phase equivalent of 500 mg/m(3) whole smoke (generated by electrostatic precipitation of particulates), or filtered air. Histopathology (1, 2, 5, 10, or 20 exposures, I and 4 wk postexposure) and cell proliferation (BrdU incorporation after 5 or 20 exposures and at 4 wk postexposure) were assessed in the nose and larynx. Blood nicotine, cotinine, and carboxyhemoglobin were monitored to substantiate exposure. Nicotine and cotinine levels were significantly elevated (p less than or equal to.05) in whole-smoke-exposed rats relative to both filtered-air- and vapor-phase-exposed rats, while blood carboxyhemoglobin was comparably increased in both whole-smoke- and vapor-phase-exposed groups. Respiratory epithelial cell necrosis was observed in the anterior nose after only a single exposure to either whole smoke or its vapor phase. Hyperplasia subsequently developed after additional exposures to whole smoke or vapor phase, with squamous metaplasia occurring in whole-smoke-exposed animals. After 20 exposures, the cell proliferation index was increased in the nasal respiratory epithelium of rats exposed to either whole smoke or smoke vapor phase, with a greater response noted in whole-smoke-exposed rats. A minimal increase in the cell proliferation index, without significant histopathology, was noted in the olfactory epithelium. Necrosis of the laryngeal epithelium was an immediate response to whole-smoke exposure. This was eventually followed by squamous metaplasia. Hyperplasia, without initial cell necrosis, was seen in the larynges of smoke vapor-phase-exposed rats. Only minimal squamous metaplasia occurred in the larynges of the vapor-phase-exposed rats. Histopathologic and proliferative responses were markedly reduced in all respiratory-tract tissues at 1 and 4 wk post-exposure. These data suggest that the morphologic changes commonly seen in the upper respiratory tract of whole-smoke-exposed rats are early adaptations related, in part, to components of the vapor phase of mainstream cigarette smoke.