Squamous Lesions in the Lungs of Rats Exposed to Tobacco-smoke-condensate Fractions by Repeated Intratracheal Instillation

Twice-weekly intratracheal instillations in rats of up to 24 mg of Fraction (R + P)G suspended in either infusine (I) or buffered saline/gelatine (BS/G) gave rise to foci of squamous metaplasia of alveolar epithelium (SqM) and squamous neoplasms (SqN). Fraction (R + P)G, which is a fraction of cigarette-smoke condensate almost as tumorigenic for mouse skin as the nearly 30 × larger mass of condensate from which it is derived, could be given in this way for up to 40 weeks without excessive mortality or any marked effect on the rate of body-weight gain. By contrast, similar treatment with Fraction N(QG), a fraction having very low tumorigenic activity for mouse skin, induced no SqN and barely any excess of SqM over that induced by either vehicle alone. The effects of Fraction (R + P)G on the incidence of SqM and SqN were both time and dose related, the effect on SqM incidence being already evident after 10 weeks of treatment. No SqN seen were unequivocally malignant, though, due to the design of the experiment, only 5 rats exposed to Fraction (R + P)G were observed more than 60 weeks after the start of the experiment. Other changes in the lung, including aggregates of alveolar macrophages laden with golden-brown pigment (GBM) and foci of cuboidal/columnar metaplasia of alveolar epithelium (CCM), were frequently seen in response to both fractions. Fraction (R + P)G administered in I was more effective in causing SqM and SqN than the same fraction administered in BS/G. The implications of the findings are discussed, particularly the possibility that the intratracheal/instillation technique might be useful as a rapid bioassay for comparing the tumorigenicity of different cigarette-smoke condensates.