title: Hypomethylation of DNA in estrogen-induced and -dependent hamster kidney tumors.
abstract: 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 11 beta-ethyl-17 alpha-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.
authors: Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
authors: L J
authors: LJ
authors: Lu
authors: J G
authors: JG
authors: Liehr
authors: D A
authors: DA
authors: Sirbasku
authors: E
authors: E
authors: Randerath
authors: K
authors: K
authors: Randerath
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004967:Estrogens; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008745:Methylation
chemical_list: D004273:DNA, Neoplasm; D004967:Estrogens; D004054:Diethylstilbestrol; D004247:DNA