The R3230AC mammary adenocarcinoma responds to estrogen treatment with lactation accompanied by marked increases in glucose-6-phosphate dehydrogenase and NADP-malic2 enzyme activities. The effect of actinomycin D on these hormoneinduced responses was studied. NADP-isocitric dehydrogenase, phosphoglucose isomerase, and phosphoglucomutase activities were also measured in the tumor as well as the RNA and DNA contents. Similar measurements were made on uteri of these animals.
Actinomycin D prevented the estrogen-induced increase in glucose-6-phosphate dehydrogenase, NADP-malic enzyme, and phosphoglucomutase activities in the tumor. The antibiotic likewise prevented the elevation of uterine glucose-6-phosphate dehydrogenase and NADP-malic enzyme activities; the prevention of these hormone responses occurred at lower doses in the uterus compared with the tumor. There was a significant decrease in RNA in the neoplasm and uterus following treatment with actinomycin D. Treatment with the antibiotic alone caused a decrease in the activities of all of the enzymes studied in the tumor and the uterus, with the exception of phosphoglucose isomerase in the neoplasm. These data indicate that the estrogen-induced enzyme activity increases resulted from DNA-directed RNA synthesis.
An unusual and interesting result was the effect of actinomycin D and estradiol valerate on some of these enzymes in normal mammary tissue. Under the conditions of these experiments, an increase in the activities of glucose-6-phosphate dehydrogenase, NADP-malic enzyme, and NADP-isocitric dehydrogenase occurred following treatment with actinomycin D in combination with estrogen, an increase that was not obtained by hormonal treatment alone. These data are discussed in light of recent data on the effects of actinomycin D on other enzymes.
This work was supported by Contract No. SA-43-ph-2395, Cancer Chemotherapy National Service Center, National Cancer Institute, NIH.
The abbreviations used are: RNA, ribonucleic acid; DNA, deoxyribonucleic acid; NADP, nicotinamide adenine dinucleotide phosphate; and NADPH, reduced form of nicotinamide adenine dinucleotide phosphate.