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7,12-Dimethylbenz[a]anthracene-induced Alteration of Mammary Epithelial Cell RNA-synthetic Patterns in Rat Strains of High and Low Tumor Incidence¹

Chemical Carcinogenesis, NCI-Frederick Cancer Research Center, Frederick, Maryland 21701

From 1 to 4 days after 20 mg 7,12-dimethylbenz[a]anthracene (DMBA) were fed to 51-day-old Sprague-Dawley rats, a high-tumor-incidence strain, the incorporation of [³H]uridine into newly synthesized rapidly labeled nucleolar and cytoplasmic RNA extracted from mammary gland epithelial cells was depressed to 60% of the control value. This decrease was followed by a 40 to 100% stimulation of cellular RNA specific activity over control values throughout the remainder of the 28-day test period. With the exception of a smaller early time period decrease, the specific activity of RNA extracted from the mammary epithelium of DMBA-treated Long-Evans rats, a low-tumor-incidence strain, was not different from control values at any of the times studied. DMBA did not alter the RNA specific activities in liver, kidney, duodenum, and mammary fibroblasts derived from either the Sprague-Dawley or Long-Evans strain. Exposure of epithelial cells to DMBA (0.05 µg/ml) for 20 hr in vitro showed a parallel early decrease of RNA specific activity in the Sprague-Dawley rats. Since the specific activity of the cytoplasmic soluble uridine pools in both the in vivo and in vitro studies remained unchanged, RNA specific activity alterations were not due to changes in the uptake of radioactively labeled precursor nucleoside into the epithelial cells. These experiments demonstrated a difference in the response of mammary gland epithelial cells derived from a high-tumor-incidence strain (Sprague-Dawley) from those isolated from a low-tumor-incidence strain (Long-Evans) when RNA metabolism was measured following a single feeding of a chemical carcinogen. The alterations in RNA-synthetic patterns were specific to the mammary epithelium and could not be demonstrated to occur in the other tissues studied. With pulse-chase radioactive labeling and polyacrylamide gel electrophoretic techniques, virgin rat mammary epithelium was shown to synthesize high-molecular-weight preribosomal RNA and process it into 18S and 28S ribosomal RNA, a series of steps previously reported to occur in the mammary gland during pregnancy and lactation.

¹ Supported by National Cancer Institute Contract N01-CO-25423 to Litton Bionetics, Inc. Presented in part at the 67th Annual Meeting of the American Association of Cancer Research in Toronto, Ontario, Canada, May 1976 (9).

² To whom requests for reprints should be addressed.

Received 3/25/77. Accepted 11/11/77.