Abstract
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, 1 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.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 wholesmoke-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 postexposure. 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.