Sequential cytological changes during development of respiratory tract tumors induced in hamsters by benzo(a)pyrene-ferric oxide.

Abstract

The exfoliative cytology of the lung was studied during the induction and early development of respiratory tract tumors. Syrian golden hamsters received multiple intratracheal injections of benzo( a )pyrene-Fe2O3 for 14 weeks at a cumulative dose of 45 mg benzo( a )pyrene. Shortly after start of the experiment a severe, probably toxic, cytological response to the carcinogen application was observed; this response rapidly diminished during further injections and disappeared after cessation of carcinogen administration. The average time interval from start of carcinogen application to death was 35.5 weeks. During this time specimens revealed a progression from mild atypia of squamous metaplastic cells, to moderate atypia, to marked atypia, to changes indicative of cancer. These carcinogen-induced progressive cytological changes showed striking morphological similarities to cytological changes described in cigarette smokers prior to the development of lung cancer. By the 25th week of the experiment, specimens of all carcinogen-treated animals had cells suggestive or conclusive of cancer. In animals that died after the 35th week, the diagnosis of cancer had been made at an average time of 19 weeks before death, while in animals that died between the 18th and 35th week of the experiment the diagnosis had not been made earlier than 9 weeks before death. Sensitivity and specificity of the cytological method for diagnosing cancer were very high, since no false negative diagnoses were made in tumor-bearing animals nor were false positive diagnoses made in control animals that received Fe2O3 alone or in carcinogen-treated animals that did not develop tumors. Cytological typing of malignant tumors was efficient for histologically well-differentiated tumor types.