Target organ-specific covalent DNA damage preceding diethylstilbestrol-induced carcinogenesis

摘要: The synthetic estrogen diethylstilbestrol (DES), a known human carcinogen, induces renal carcinoma in male Syrian hamsters within 6 months after s.c. implantation. Tumor formation could be evoked by its hormonal properties or reactive genotoxic metabolite binding to DNA, but previous attempts detect adducts have failed. In the present study, kidney DNA of hamsters, treated with DES implants induce carcinoma, was analyzed for presence DES-induced using 32P-postlabeling assay. Covalently-modified nucleotides were detected kidneys chronic treatment, not untreated liver tumor tissue DES-treated animals. This report demonstrates first time ability an give rise covalent modification vivo specifically target organ carcinogenesis. are taken as evidence initiation via damage cellular macromolecules, addition tumor-promotional effects described previously.