Inhibition by an aromatic retinoid of DNA damage induced by the bladder carcinogen N-butyl-N-(3-carboxypropyl)nitrosamine.

The reversible inhibitory action of an aromatic analog of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (aromatic retinoid) on bladder carcinogenesis was studied by biochemical and histopathological methods. fischer 344 female rats were fed a diet containing the aromatic retinoid (0, 12.5 or 50 ppm) for 56 days. On day 57, 60 or 70, 50 mg/kg body weight of N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) in a volume of 0.3 ml was directly instilled intravesically through a urethral catheter. DNA damage in rat bladder epithelial cells 2, 24 and 48 hr after administration of BCPN was examined by measuring the change in sedimentation profile of the DNA in 5 approximately 20% alkaline sucrose gradients. DNA sedimentation was measured by a fluorometric procedure. Histopathological examination of the bladder epithelium was performed at the same time. Two hours after a 5-min exposure to BCPN, DNA damage at the urothelium was observed in rats fed the diet without the aromatic retinoid, but the damage was repaired after 24 and 48 hr. The highest dose of the aromatic retinoid almost completey prevented DNA damage by BCPN on days 57 and 60. A lower dose of the aromatic retinoid did not prevent DNA damage by BCPN on days 57, 60, and 70, while the higher dose did not prevent damage by BCPN on day 70. No histological changes were observed in the urothelium of rats treated with the aromatic retinoid and BCPN, and electron microscopy showed that the epithelium also remained normal. DNA damage was induced by BCPN at the urothelium, and the damage was inhibited by previous administration of the aromatic retinoid.