Abstract
Analgesic abuse can lead to renal papillary necrosis (RPN) and subsequently to upper urothelial carcinoma (UUC). Ultrastructural changes in renal papillary necrosis and upper urothelial carcinoma were studied in rats. RPN was induced using a papillotoxin; -bromoethanamine hydrobromide (BEA) and UUC was initiated using low dose of a bladder carcinogen; N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). A single intraperitoneal injection of BEA resulted in cellular swelling and damage to interstitial cells, collecting ducts, mitochondria, capillaries , renal concentration mechanism and the thin limbs of Henle. RPN was present in most rats by 12hr after treatment. The thin limbs of Henle were the last structures to show damage. Damage to interstitial cells, collecting duct cells and mitochondria occurred before the concentration mechanism was significantly damaged. The swelling of cells resulted in complete or partial closure of ducts of Bellini. It was concluded from this results that (1) since the concentration mechanism was still intact when interstitial cells , collecting duct cells and mitochondria were damaged, damage to these structures could be by cytotoxicity as a result of hyperconcentration of BEA at the papilla. (2) This initial cytotoxic damage would be followed by a secondary damage of medullary ischaemia as a result of the damaged interstitial cells and collecting ducts (sites of prostaglandin synthesis) and pressure exerted on the capillary walls by swollen collecting duct cells. (3) That the cortical tubule dilation often associated with analgesic nephropathy and experimentally-induced RPN, could have been brought about by the back pressure created in those tubules whose ducts of Bellini were blocked by swollen cells. Urothelium initiated with low doses of BBN was promoted to carcinogenesis following a single ip dose of BEA. It was suggested from this result that if, as has frequently been proposed, BEA behaves similarly to analgesics, then this implies that analgesics are either complete carcinogen (since they seem capable of initiating and promoting the urothelium to carcinogenesis) or that analgesics could merely be promoters which, following abuse, induce upper urothelial carcinoma only in people with prior initiated urothelium as a result of exposure to carcinogenic environmental contaminants such as nitrosamines, rubber, dye and cigarette smoke.