COMPARISON OF DNA REACTIVITY OF THE POLYPHENYLETHYLENE HORMONAL AGENTS DIETHYLSTILBESTROL, TAMOXIFEN AND TOREMIFENE IN RAT AND HAMSTER LIVER

The polyphenylethylene estrogenic drug diethylstilbestrol and a struct ural analogue tamoxifen have been found to be hepatocarcinogenic in fe male rats, whereas another analogue, toremifene, did not induce liver tumors. The P-32 post-labelling technique for detection of DNA adducts was used to investigate the DNA reactivity of these three hormonal ag ents in the livers of female Sprague-Dawley rats and Syrian hamsters. Adducts were quantified using a radioanalytic imaging system in compar ison with the standard Cerenkov assay. With administration of the chem icals at several doses by daily gavage to rats for 10 days and to hams ters for 7 days, tamoxifen was found to produce five adducts in rat li ver and six adducts in hamster liver. The amounts of adducts were dose related from 10 to 90 mu mol/kg per day in rats and from 17 to 160 mu mol/kg per day in hamsters. The two methods of quantification yielded comparable results. Under these conditions, neither toremifene nor di ethylstilbestrol produced adducts in rats and diethylstilbestrol produ ced none in hamsters. We conclude that tamoxifen is highly DNA reactiv e in the species studied and that this is likely to be involved in its strong carcinogenicity in rat liver.