Dose responses of R3230AC mammary tumor and mammary tissue to estrogen: enzymes, nucleic acids, and lipids.

Abstract

The effect of several dose levels of estradiol valerate on the activities of 6 enzymes and the levels of nucleic acids and certain lipids was studied in a transplantable lactating mammary adenocarcinoma, R3230AC, as well as in the mammary glands of the same tumor-bearing animals. Estrogen treatment caused a doserelated increase in the activities of glucose-6-phosphate dehydrogenase, malate dehydrogenase (decarboxylating), and phosphoglucomutase in the neoplasm, whereas it decreased the activities of glucosephosphate isomerase and isocitrate dehydrogenase in that tissue. Glycerolphosphate dehydrogenase activity decreased markedly as the dose of estrogen increased. The tumor contained elevated levels of free fatty acids and triglycerides as well as slightly decreased DNA levels, these changes being related to the dose of hormone administered. All enzyme activities increased in the mammary glands following treatment with estrogen. Cholesterol, but neither free fatty acids nor triglycerides, increased as the dose of estradiol valerate increased. Both RNA and DNA levels likewise rose relative to the dose of the hormone. Enzyme activity of mammary tissue expressed in terms of DNA concentration indicated that only glucose-6-phosphate dehydrogenase and malate dehydrogenase (decarboxylating) activities remained elevated at the higher doses of hormone, whereas both glucosephosphate isomerase and glycerolphosphate dehydrogenase activities decreased at these doses. In a similar manner, free fatty acids/mg DNA and triglycerides/mg DNA decreased by high doses of estrogen, but cholesterol/mg DNA remained constant. The lipid metabolism as well as the similarities and differences of the responses of normal and neoplastic tissue to estrogen are discussed.