Shafie S M, Cho-Chung Y S, Gullino P M
Cancer Res. 1979 Jul;39(7 Pt 1):2501-4.
Approximately 70% of primary 7,12-dimethylbenz(alpha)-anthracene-induced mammary tumors regressed when (tumor-bearing) rats were made diabetic after treatment with streptozotocin. In the intact animal, cyclic adenosine 3':5"-monophosphate (cAMP) levels of tumors that regressed following the induction of diabetes were initially 4-fold lower than in unresponsive tumors but increased 4-fold during regression. The insulin-independent tumors showed no statistically significant changes. cAMP binding in cytosol of regressing tumors was about 80% above the initial values at 36 hr after therapy but decreased to about 45% 1 week later. On the contrary, the binding capacity of the nuclei showed a 56% increase at 36 hr and increased gradually to about 3-fold 1 week later. Within 36 hr after treatment, total histone kinase activity increased 127% in the cytosol and 153% in the nuclei of regressing tumors. The increment of histone kinase activity was almost totally in the cAMP-dependent component of the enzyme. These changes were not apparent in insulin-independent tumors. The results are interpreted to indicate that mammary tumor regression due to diabetes involves the cAMP system and occurs through a sequence of events similar to those observed during regression induced by either ovariectomy or dibutyryl cAMP (cyclic adenosine 3':5'-monophosphate) treatment.
在用链脲佐菌素治疗使（荷瘤）大鼠患糖尿病后，约70%的原发性7,12 - 二甲基苯并（α）蒽诱导的乳腺肿瘤发生了消退。在完整动物中，糖尿病诱导后消退的肿瘤的环磷酸腺苷（cAMP）水平最初比无反应的肿瘤低4倍，但在消退过程中增加了4倍。非胰岛素依赖型肿瘤未显示出统计学上的显著变化。消退肿瘤细胞质中cAMP结合在治疗后36小时比初始值高出约80%，但1周后降至约45%。相反，细胞核的结合能力在36小时时增加了56%，并在1周后逐渐增加至约3倍。治疗后36小时内，消退肿瘤细胞质中的总组蛋白激酶活性增加了127%，细胞核中增加了153%。组蛋白激酶活性的增加几乎完全在该酶的cAMP依赖性组分中。这些变化在非胰岛素依赖型肿瘤中不明显。结果被解释为表明糖尿病导致的乳腺肿瘤消退涉及cAMP系统，并且是通过一系列类似于卵巢切除或二丁酰cAMP（环磷酸腺苷3':5'-单磷酸）治疗诱导的消退过程中所观察到的事件发生的。
