Different endocrinological properties, growth rate and sensitivity to chemotherapy of aplastic mammary carcinoma in normo- and hypoglycemic phase of tumor growth.
An aplastic mammary carcinoma (AMC) grew slower in hypoglycemic mice (caused by fasting or by daily insulin injections) and in hyperglycemic mice (caused by alloxan or streptozotocin, or by daily injections of glucose) than in normoglycemic mice. The tumor was able to adapt to the unfavourable conditions of the diabetes; cells, when transplanted from diabetic donors into diabetic recipients, secreted immunoreactive insulin (IRI) and immunoreactive glucagon (IRG), which are deficient in the diabetic hosts. In the terminal (hypoglycemic) phase of tumor growth, the concentrations of glucose, IRI and IRG decreased. The immunological reactivity of the host animals was reduced in the hypoglycemic terminal phase. The tumor cells taken from hosts in this phase behaved differently from the cells taken in the normoglycemic phase. The "hypoglycemic" cells grew more slowly in healthy mice; the intensity of their DNA synthesis was diminished, their response to antitumor therapy was weaker. Furthermore, it was necessary to transplant more of these cells to obtain tumors in all recipients, and they lost their ability to adapt to diabetic conditions (i.e. secreted neither IRI nor IRG). Hypoglycemia was apparently the immediate cause of death in mice with AMC. Injections of glucose or glucagon into mice with AMC eliminated the hypoglycemia temporarily and postponed the death by 4 days. Mice treated with glucagon and with chemotherapy or immunotherapy survived 6-9 days longer than mice treated with chemo- or immunotherapy alone. Some of these differences between the end-stage and the progressively growing tumors could be explained in terms of tumor cell kinetics but some could be attributed to metabolic conditions of the host caused in part by the tumor.
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications; D007003:Hypoglycemia / Q000150:complications*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation
D004273:DNA, Neoplasm; D007328:Insulin; D003520:Cyclophosphamide; D005934:Glucagon