The utilization of glucose-1-14C, -6-14C, -6-3H, and acetate-1-14C was studied in slices of normal gland, both suckled and nonsuckled; outgrowths of hyperplastic alveolar nodules (HAN's); and mammary adenocarcinomas excised from pregnant and lactating C3H mice. The major metabolic products (CO2, lipids, fatty acids, and lactate) of these substrates were isolated and assayed for radioactivity.
With the exception of lactate production, normal lactating glands showed the highest metabolic activity in all the parameters studied, uptake of substrates, production of CO2, lipogenesis, and pentose phosphate cycle activity. Slices of HAN outgrowth and of nonsuckled, normal tissue from lactating mice exhibited very similar metabolic activity, which was lower than that of the normal, suckled gland. Tumor slices exhibited the lowest metabolic activity of the tissues studied from lactating mice. Lactate accumulation from glucose was observed in normal, nonsuckled tissue and in HAN outgrowth, as well as in adenocarcinoma.
While the addition of glucose to neoplastic slices stimulated incorporation of acetate into fatty acids, the extent of stimulation was much less than that observed in normal, lactating tissue from the same animal. Slices of the HAN outgrowth and of the nonsuckled, normal tissue from lactating mice also responded to the addition of glucose by increasing acetate conversion to fatty acids; the extent was intermediate between that exhibited by the normal tissue and by the adenocarcinoma.
The metabolic activity of all tissues excised from pregnant mice was lower than that of tissues from lactating mice. Therefore, the metabolism of the HAN outgrowth and of the adenocarcinoma is influenced by the physiological state of the host. The manner and means of glucose and acetate utilization by normal glandular tissue from pregnant mice was very similar to that by the HAN outgrowth from the same animals. Again, the tumor was the least active tissue studied.
The type of lipid synthesized from acetate-1-14C by normal glandular tissue and by HAN outgrowth from pregnant mice was similar, 40 to 50% of the labeled lipid being triglyceride. The onset of lactation increased the percentage of incorporation into triglyceride almost two-fold in both the normal and preneoplastic tissues.
The types of fatty acids synthesized from acetate-1-14C by slices of normal glands, of HAN outgrowths, and of adenocarcinomas prepared from tissues taken from pregnant mice were similar, predominantly 16 carbons long. Slices of normal gland, both suckled and nonsuckled, from lactating mice produced mainly 14C fatty acids 10 to 12 carbons long. In contrast, the type of fatty acids produced by the HAN outgrowth and by the tumor was less responsive to the onset of lactation. The fact that the HAN outgrowth cannot produce the pattern of fatty acids typical of the lactational state is the first indication that this preneoplastic tissue is metabolically distinct from comparable normal mammary gland tissue.
This investigation was supported by USPHS Research Grant CA-11736 from the National Cancer Institute and Grant P182-I from the American Cancer Society. This is the 3rd in the series, “Metabolic Characteristics of a Naturally Occurring Preneoplastic Tissue.”