F. Montandon et Gm. Williams, COMPARISON OF DNA REACTIVITY OF THE POLYPHENYLETHYLENE HORMONAL AGENTS DIETHYLSTILBESTROL, TAMOXIFEN AND TOREMIFENE IN RAT AND HAMSTER LIVER, Archives of toxicology, 68(4), 1994, pp. 272-275
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.