The progression of pulmonary
neoplasia was examined in strain A/J male mice treated with a single dose of
vinyl carbamate (60 mg/kg, i.p.) 6 weeks after birth. Interim sacrifices were performed at 7, 8, 10, 12, or 14 months. Proliferative lesions of the lung were divided into four categories:
hyperplasias,
adenomas,
carcinomas arising within
adenomas, and
carcinomas. Grossly visible surface
tumor counts, histologic diagnoses, and morphometric measurements of histologic lesions were used to evaluate progression.
Vinyl carbamate-treated mice showed increased mean surface
tumor counts at all time points. Diagnostic evaluation suggested that as a function of time, the relative frequency of
hyperplasias decreased and the relative frequency of
adenomas increased. The relative frequency of
adenomas subsequently decreased, whereas the relative frequency of
carcinomas increased. At all time points,
carcinomas arising within
adenomas were present. As time progressed, the number of
carcinomas arising within
adenomas decreased, whereas the number of "pure"
carcinomas increased. Morphometric analysis of lesions indicated
hyperplasias to be small, that
adenomas were larger than
hyperplasias, and
carcinomas were larger than
adenomas and
hyperplasias, suggesting that few
adenomas or
carcinomas arise de novo. Collectively, these data suggest that the majority of pulmonary
tumors in A/J mice treated with
vinyl carbamate arise as
hyperplasias, progress to
adenomas, and ultimately result in
carcinomas.