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Ann Thorac Surg 1984;38:627-632
© 1984 The Society of Thoracic Surgeons
Divisions of Surgery, Anatomic Pathology, and Cytogenetics and Cytology, City of Hope National Medical Center, Duarte, CA
* Address reprint requests to Dr. Benfield, City of Hope National Medical Center, Duarte, CA 91010
A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[a]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean ± standard deviation [SD], 3.77 ± 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean ± SD, 6.48 ± 3.6). These differences are significant (p < 0.05). We conclude that the developmental continuum of epidermoid lung cancer can now be reproduced in controlled, predictable fashion in hamsters.
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