Morphological changes in the basement membrane during progression from non-invasive to invasive rat bladder cancer induced by N-butyl-N-(4-hydoxybutyl) nitrosamine.

Abstract

To investigate the ultrastructural changes in the basement membrane (BM) in the rat model of bladder cancer when progressing from non-invasive to invasive disease. N-butyl-N-(4-hydoxybutyl) nitrosamine (BBN) was administered to 50 rats (7 weeks old) in their drinking water (0.05% BBN) for 28 weeks. At between 20 and 28 weeks, 10 rats were killed every 2 weeks and morphological changes of the BM were investigated by transmission electron microscopy and histological changes by light microscopy. At between 20 and 28 weeks, the transitional cell carcinoma (TCC) of the rat bladder induced by BBN progressed from non-invasive (stage Ta) to invasive (stage T1-2) disease. Focal thinning and discontinuity of the BM occurred in five of 26 rats with non-invasive TCC and in all 24 rats with invasive TCC. Stage Ta bladder cancer in the rat model may be associated with degradative changes in the BM and can be divided into two types, Ta1 where there is no degradation of the BM and Ta2, where the BM is degraded.