Induction of Lung Cancers in Preselected, Localized Sites in the Dog23

Abstract

Cancers were induced in 10 dogs in preselected sites within the lung. These 10 animals were among 89 dogs enrolled in 10 protocols with different carcinogens, doses, and techniques over 6 years. The 10 dogs that developed cancers were included in five of these protocols; 4 of the cancers were included in one of the protocols. The administered carcinogens included the aromatic hydrocarbons benzo[a]pyre ne (BP), N-methyl-N-nitrosourea (MNU), 7,12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (MCA), and yttrium-91 (⁹¹Y) beta radiation. The techniques of application included intrabronchial and intrapulmonary sustained-release implants of DMBA and⁹¹Y, serial intrabronchial submucosal injections of BP, DMBA, and MCA, or topical application of MNU. The intervals from the first application of a carcinogen to the diagnosis of malignant disease ranged from 8 to 56 months. Of the tumors induced, 9 were centrally located squamous cell carcinomas and 1 was a peripherally located carcinosarcoma. Four of the dogs were killed or died with stage 3 disease. The remaining 6 dogs are alive and are being evaluated serially; all 6 are in stage 1.