SUBLETHAL ALTERATIONS AND SUSTAINED CELL-PROLIFERATION ASSOCIATED WITH THE DIETHYLSTILBESTROL-INDUCED RENAL CARCINOGENESIS IN MALE SYRIAN GOLDEN-HAMSTERS

The current study was initiated to explore the sublethal alterations a nd the tissue damage occurring in the hamster kidney during diethylsti lbestrol-induced renal carcinogenesis. A total of 49 male Syrian golde n hamsters (36 treated and 13 control animals) was utilized in the exp erimental procedure. Chronic exposure to diethylstilbestrol was achiev ed by s.c. insertion of implants containing 25 mg diethylstilbestrol. For long-term observation, adequate blood level of diethylstilbestrol was insured by renewing the implant every 2 months. Experimental group s (n = 4 to 9) were terminated 1, 2, 4, 6, 9 and 11 months after initi al implantation for morphological examination of the kidney. Diethylst ilbestrol carcinogenicity in this experimental model was confirmed by the observation that most animals undergoing drug exposure for 6 month s or more exhibited renal neoplasms. The most striking nonneoplastic m orphological abnormality disclosed by histological and cytological exa mination consisted in the accumulation of granular inclusions in proxi mal tubule cells. In renal tissue, the extent of cell proliferation de termined by PCNA labeling progressively increased along with the durat ion of diethylstilbestrol exposure and suggested a sustained prolifera tive response in altered proximal tubules. The present data suggest th at an impairment of functional tubular regeneration could promote, as well as the estrogen genotoxic effect, the tumorigenicity of diethylst ilbestrol in the kidney of male hamsters.