Inhibitory effect of an aromatic retinoic acid analog on urinary bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

Abstract

The inhibitory effect of an aromatic retinoic acid analog, ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate, on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was evaluated. Administration of 50 ppm of aromatic retinoid in the diet before BBN in the drinking water reduced the incidence of papillary or nodular hyperplasia as a preneoplastic lesion of the bladder epithelium (P < 0.05). When given before, during or after BBN, it also greatly reduced the incidence of papilloma (P < 0.001 before BBN, P < 0.01 during or after BBN treatment), and slightly inhibited the development of cancer. Administration of 100 ppm of aromatic retinoid before or during BBN administration also reduced the incidences of papillary or nodular hyperplasia (P < 0.01 before BBN, P < 0.05 during BBN treatment), and its administration before, during or after BBN treatment greatly reduced the incidences of papilloma (P < 0.001), and cancer (P < 0.01 before or after BBN, P < 0.001 during BBN treatment). Similar results were obtained by assessing the effect of the retinoid on the average numbers of various epithelial lesions per 10 cm length of basement membrane of the bladder in tissue slices. These results show that the aromatic retinoid inhibits both the initiation and promotion of bladder carcinogenesis induced in rats by BBN, and that its effect is dose-dependent.