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Influence of Insulin on Growth and Metabolism of 7,12-Dimethylbenz(a)anthracene-induced Mammary Tumors¹

Department of Biochemistry and University of Rochester Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642

The influence of insulin on growth and carbohydrate metabolism of 7,12-dimethylbenz(a)anthracene- (DMBA) induced mammary tumors was examined. Approximately 60% of the DMBA-induced tumors regressed after the animals were made diabetic by streptozotocin treatment, a pattern of tumor growth that was reversed by administration of 2 IU of insulin per day to diabetic rats. DMBA-induced tumors regressing in diabetic animals, termed insulin dependent, demonstrated significant decreases in the activities of pyruvate kinase, phosphofructokinase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Tumors that continued to grow in diabetic rats, termed insulin independent, showed enzyme activities similar to those of growing tumors in intact animals. Examination of utilization of labeled glucose in vitro by slices of tumors regressing in diabetic rats indicated that there was a decrease in both the pentose phosphate pathway and the glycolytic pathway, on the basis of ¹⁴CO₂ production and incorporation into fatty acids of labeled glucose substrate. Thus, tumor regression and reduced carbohydrate metabolism appear to be correlated among those carcinomas that have been termed insulin dependent, suggesting that insulin should be considered as another hormonal factor in DMBA-induced breast cancers.

¹ This research was supported by USPHS Grants CA 12836 and CA 11198 and by a grant from the Monroe County Cancer and Leukemia Association.

² Submitted in partial fulfillment of the requirements for the Ph.D. degree. Present address: Department of Biochemistry, Case Western Reserve University, School of Medicine, Cleveland, Ohio.

³ To whom requests for reprints should be addressed.

Received 2/13/74. Accepted 8/23/74.