DNA Adduct Profiles in Hamster Kidney Following Chronic Exposure to Various Carcinogenic and Noncarcinogenic Estrogens

Summary

The generation of specific estrogen-induced DNA adduct modifications in the hamster kidney following chronic exposure has been reported. Moreover, these covalent DNA alterations produced by estrogens have been suggested to play a critical role in estrogen-induced renal tumorigenesis in this species. Employing the P-1 nuclease postlabeling methods, we have studied the generation of DNA adduct modifications by various strongly carcinogenic (Ethinylestradiol, EE) and noncarcinogenic (17α-estradiol, β-dienestrol, indanestrol) estrogens and compared these data to untreated or cholesterol-treated castrated male hamsters at 5.0 and 7.0 months. No significant differences were found between DNA adduct profiles (∼ 10 spots) in these control groups and those generated from any of the estrogenic compounds tested, whether carcinogenic or not. These data coupled with the very poor metabolism of Moxestrol (1lβ-methoxy EE) seen in the hamster kidney weaken the view for a significant role for renal DNA adduct alterations, which appears evidently indigenous, in the estrogen-induced neoplastic transformation of the hamster kidney.