The Annals of Thoracic Surgery, Vol 32, 592-601, Copyright © 1981 by The Society of Thoracic Surgeons
A clinically relevant canine lung cancer model
JR Benfield, EC Shors, WG Hammond, RR Paladugu, AH Cohen, T Jensen, PC Fu, HY Pak and RL Teplitz
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,
dimethylbenzanthracene, 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.
