Apoptosis and carcinogenesis: morphologic observations in the rat bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

Abstract

We investigated the role of apoptosis in rat bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Apoptosis was detected in BBN-induced rat bladder lesions by routine hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and transmission electron microscopic examinations. After administration of BBN, various pathologic changes were observed in the rat bladder after intervals of between 4 and 28 weeks. Through a comparative study in serial sections, the incidence of apoptosis, detected by either routine H&E staining or TUNEL staining, displayed marked elevation in BBN-induced rat bladder lesions, as compared to that in the normal epithelium of the rat bladder, particularly in invasive transitional cell carcinoma. Apoptotic cells with different morphologic features were ultrastructurally demonstrated in a series of rat bladder lesions. Significant group differences in the incidence of apoptosis were seen among the BBN-induced lesions and the normal epithelium of the rat bladder, and among the invasive transitional cell carcinomas and other lesions, before the tumor cells were seen to invade the rat bladder. Our data suggest that apoptosis may be closely related to carcinogenesis and tumor invasion of the rat bladder induced by BBN, and that the comparative study of serial sections, each stained by H&E and TUNEL, combined with electron microscopic observation, may provide the most reliable informations in semiquantitative assessment of apoptosis.