A Clinically Relevant Canine Lung Cancer Model

Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo-[a]pyrene, nitrosomethylurea, dimethylbenzanthra-cene, and methylcholanthrene, singly or in combinations. Sustained-relea...

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Published inThe Annals of thoracic surgery Vol. 32; no. 6; pp. 592 - 601
Main Authors Benfield, John R., Shors, Edwin C., Hammond, William G., Paladugu, Rao R., Cohen, Arthur H., Jensen, Thomas, Fu, Paul C., Pak, Hyun Y., Teplitz, Raymond L.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Inc 01.12.1981
Subjects
9,10-Dimethyl-1,2-benzanthracene
Animals
Benzo(a)pyrene
Benzopyrenes
Carcinogens
Delayed-Action Preparations
Disease Models, Animal
Dogs
Lung Neoplasms - chemically induced
Methods
Methylcholanthrene
Methylnitrosourea
Neoplasms, Experimental - chemically induced
Radioisotopes - administration & dosage
Tetradecanoylphorbol Acetate
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Summary:Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo-[a]pyrene, nitrosomethylurea, dimethylbenzanthra-cene, and methylcholanthrene, singly or in combinations. Sustained-release discs were placed into lung parenchyma or sutured into major bronchi. Tracheal segments were isolated as cervical pedicle grafts. Gross and histological evolution was reproducible. Columnar and basal hyperplasia and squamous metaplasia were early changes. Atypia occurred within 6 weeks and was found in all dogs within 16 to 18 weeks. Invasive cancers occurred within 8 to 65 months. No tracheal graft developed cancer. Of 15 dogs with parenchymal sustained-release implants, 1 to date has developed cancer in 8 months. Four endobronchial regimens have produced 16 cancers in 56 lungs at risk for 18 to 65 months. No cancers developed in 23 lungs at risk from eight other regimens. Of 10 dogs at risk for unilateral endobronchial cancer, 5 have had cancer. Of 23 dogs with both lungs at risk, 9 developed cancer. We have shown focal carcinogenesis with well-defined pathogenesis and an extended preneoplastic period at predictable sites in a lung cancer model.
ISSN:0003-4975
1552-6259
DOI:10.1016/S0003-4975(10)61804-8