Hypomethylation of DNA in estrogen-induced and -dependent hamster kidney tumors

The development and maintenance of DNA hypomethylation were investigated in male Syrian hamsters during the course of induction of renal carcinoma by estrogens and in an estrogen-dependent tumor derived from H-301 cells. The H-301 cell line was obtained from a primary renal carcinoma induced by E-diethylstilbestrol treatment. Covalent DNA modifications in estrogen-exposed kidney and tumor tissues were also examined. The five tumors investigated were induced by s.c. estrogen treatment of animals for 7-9 months. Covalent DNA adducts were detected in kidneys after 5-7 months of exposure to various estrogens, but not in primary tumors induced by estrogen treatment for 7-9 months. Estrogen-induced covalent DNA modifications likewise were not detectable in tumors grown in estrogenized hamsters inoculated with H-301 cells. In contrast, DNA was hypomethylated in primary tumors induced by E-diethylstilbestrol, estradiol or 11β-ethyl-l7α-ethinyl estradiol, but not in untreated and estrogen-exposed kidney. Compared with kidney tissue, there was an 11-24% decrease in total genomic DNA methylation in the estrogen-induced and -dependent tumors. DNA hypomethylation was maintained in tumors derived from H-301 cells. Discontinuation of estrogen treatment rapidly decreased the size of estrogen-dependent H-301 tumors, but did not affect the degree of DNA hypomethylation. Thus, DNA hypomethylation occurred in hormone-dependent primary neoplasms and was maintained after serial transplantations independent of the growth status.