Structural alterations within N-nitrosomethylurea-induced mammary tumors after in vivo treatment with cis-hydroxyproline.

N-Nitrosomethylurea-induced mammary tumors in Buffalo rats were examined ultrastructurally and compared with tumors from rats treated in vivo for 9 days with cis-hydroxyproline (CHP). The tumors from untreated animals were heterogeneous histologically but often had their cells arranged in clusters called pseudolobules. At the periphery of the pseudolobules in control tumors, a few myoepithelial cells showed evidence of basal lamina secretion. Outlining the pseudolobules were many mast cells. Treatment with CHP inhibited the growth of the tumors. It increased the extent of atrophy and regression and also induced cyst-like areas to form within the pseudolobules. These "pseudocysts" were actually part of the stromal compartment and they sometimes contained multilayered basal lamina and mast cells. The extensive multilayering of the basal lamina observed after CHP-treatment was thought to arise from extensive infoldings as the pseudolobules "shrank" due to atrophy and loss of cells. The multilayering and cell debris disappeared from the pseudocysts, leaving many spaces bounded by myoepithelial cells. The remaining myoepithelial cells appeared atrophied, but often had an expanded rough endoplasmic reticulum. We did not observe evidence of basal lamina secretion by cells in treated tumors, which correlates with CHP's ability to block type IV collagen production.