DNA synthesis and scanning electron microscopic lesions in renal pelvic epithelium of rats treated with bladder cancer promoters

Abstract

The proliferation response of rat renal pelvic epithelium, lined by transitional epithelium, to administration of various bladder cancer promoters was investigated. In addition, prostaglandin E 2 (PGE 2), lipid peroxide (LPO), malondialdehyde (MDA) and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels were assessed in urine of rats given the non-promoter l-ascorbic acid (AsA) and the promoters sodium l-ascorbate (AsA-Na) or sodium bicarbonate (NaHCO 3) for 4 or 8 weeks. DNA synthesis in the renal pelvic epithelium, as assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation, was increased in the groups given AsA-Na, an extremely high dose of sodium chloride (NaCl), tert-butylhydroquinone (TBHQ) or ethoxyquin (EQ). Moreover, with the exception of AsA-Na, ail treatments that induced an elevation of DNA synthesis also caused morphological epithelial alterations as observed by scanning electron microscopy (SEM). Treatment with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) did not result in any proliferative response of the rat renal pelvis. No treatment-related changes in urinary PGE 2 and cyclic AMP were noted, although AsA-Na and AsA but not NaHCO 3 reduced levels of LPO and MDA in the urine. The results indicate that while the response of renal pelvic epithelium to certain bladder cancer promoters is similar to that of the bladder itself, none of the urinary cellular growth or free radical biochemical parameters is directly related to urothelial cell proliferation.