CIGARETTE-SMOKE VAPOR-PHASE EFFECTS IN THE RAT UPPER RESPIRATORY-TRACT

The temporal and regional cytotoxic and proliferative potential of who le smoke or the vapor phase of smoke from reference cigarettes was inv estigated. 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 part iculates), or filtered air. Histopathology (1, 2, 5, 10, or 20 exposur es, I and 4 wk postexposure) and cell proliferation (BrdU incorporatio n after 5 or 20 exposures and at 4 wk postexposure) were assessed in t he nose and larynx. Blood nicotine, cotinine, and carboxyhemoglobin we re monitored to substantiate exposure. Nicotine and cotinine levels we re significantly elevated (p less than or equal to.05) in whole-smoke- exposed rats relative to both filtered-air- and vapor-phase-exposed ra ts, while blood carboxyhemoglobin was comparably increased in both who le-smoke- and vapor-phase-exposed groups. Respiratory epithelial cell necrosis was observed in the anterior nose after only a single exposur e to either whole smoke or its vapor phase. Hyperplasia subsequently d eveloped after additional exposures to whole smoke or vapor phase, wit h 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 signific ant histopathology, was noted in the olfactory epithelium. Necrosis of the laryngeal epithelium was an immediate response to whole-smoke exp osure. This was eventually followed by squamous metaplasia. Hyperplasi a, without initial cell necrosis, was seen in the larynges of smoke va por-phase-exposed rats. Only minimal squamous metaplasia occurred in t he larynges of the vapor-phase-exposed rats. Histopathologic and proli ferative responses were markedly reduced in all respiratory-tract tiss ues at 1 and 4 wk post-exposure. These data suggest that the morpholog ic 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.