Covalent binding of diethylstilbestrol to microsomal protein in vitro correlates with the organotropism of its carcinogenicity.

[14C]Diethylstilbestrol (DES) was incubated in vitro with liver and kidney microsomes from male and female hamsters and rats, and the extent of non-extractable binding of radioactivity to microsomal protein was determined. Binding to microsomes from male hamster kidney, which is a target organ for DES carcinogenicity in vivo, was found to be 5-10 times higher than binding to microsomes from non-target tissues. Pretreatment with phenobarbital led to a marked increase in binding of DES to kidney microsomes but not to liver microsomes from female hamsters and male and female rats. The correlations of in vitro covalent binding with organ susceptibility implies a role for metabolic activation of DES in the mechanism of its carcinogenicity.