Effect of Sialoadenectomy on the Ability of Mouse Serum to Induce Deoxyribonucleic Acid Synthesis in Mammary Epithelial Cells: Possible Role of Epidermal Growth Factor

Abstract

Serum was collected from sham-operated or sialoadenectomized mice and added to serum starved cultures of normal mouse mammary epithelial cells. Synthesis of DNA, estimated with a pulse of 1 μmI/cro;Ci/ml [3H]thymidine between 17 and 18h after adding serum, was increased by serum. Sialoadenectomy did not affect the ability of low serum concentrations (<4%) to increase DNA synthesis, but DNA synthesis induced by higher serum concentrations was reduced by sialoadenectomy. Physiological concentrations of epidermal growth factor restored the ability of serum from sialoadenectomized mice to increase DNA synthesis. Antiepidennal growth factor reduced DNA synthesis in cultures treated with high concentrations of serum from sham-operated mice, but not in cultures treated with serum from sialoadenectomized mice. Time course studies indicated that the time of maximum DNA synthesis was similar between cultures treated with serum from sham-operated and sialoadenectomized mice. Treatment with serum from sialoadenectomized mice for 4 d resulted in lower cell number than did treatment with serum from sham-operated mice. This effect of sialoadenectomy could be overcome by epidermal growth factor. These data indicate that sialoadenectomy, which has previously been shown to depress mammary gland development, alters the endocrine status of mice, such that serum from sialoadenectomized mice is less effective in inducing DNA synthesis by mammary epithelial cells. These differences in ability of serum to induce DNA synthesis can be explained by differences in epidermal growth factor concentration or the concentration of epidermal growth factor-like constituents.