INORGANIC TIN - A NEW SELECTIVE INDUCER OF THE MURINE COUMARIN 7-HYDROXYLASE (CYP2A5)

The coumarin 7-hydroxylase of mice (Coh, CYP2A5) is known to be highly selectively inducible by both a set of heavy metals such as cobalt, i ndium and cerium and a variety of organic nitrogen-containing heteroar omatic compounds such as 3-amino-1,2,4-triazole, pyrazine and pyrazole . The investigations presented reveal that inorganic divalent tin has to be included in the list of selective inducers. Pretreatment of NMRI -mice with 50 mg SnCl2/kg body weight, daily for 2 days, increases the coumarin hydroxylation 40- and 20-fold in the kidney and liver, respe ctively. So far, the inducing potency of tin chloride is higher than t hat of the agents already known. The diagnostic inhibitor metyrapone s trongly inhibits the coumarin model reaction. In the kidneys tin gener ates an almost pure fraction of a cytochrome P450 isozyme catalyzing t he metabolism of coumarins, as inhibition experiments reveal.