The potent induction of intestinal heme oxygenase by the organotin compound, bis(tri-n-butyltin)oxide

Oral administration of bis(tri-n-butyltin)oxide, an important organotin biocidal agent, produces a substantial elevation in heme oxygenase activity when measured at 16 hours in rat small intestine. An apparent Km for hemin of 100 μM is the same in both control and the organotin-induced 9,000 × g supernatant preparations. Concomitant with elevated heme oxygenase activity there occurs a substantial reduction in benzo(a)pyrene hydroxylase activity (∼20% of controls) and cytochrome P-450 concentration (∼60% of controls). These perturbations of heme metabolism in intestinal epithelium of the rat define an important new toxicological effect of organotins and raise the possibility that concurrent oral ingestion of environmental pollutants can directly affect the cytochrome P-450-dependent metabolism of other chemicals in the intestine.