Glucagon control of carcinogenesis

Long term administration of glucagon markedly enhanced carcinoma formation in mice simultaneously treated with a chemical carcinogen, 3-methylcholanthrene (3-MCA). The number and size of squamous cell carcinomas were 3-fold greater compared to those in mice treated with MCA alone. DNA labeling and the percentage of [3H]thymidine-labeled cells were also 2- to 3-fold higher in glucagon- and MCA-treated mice than in those treated with MCA only or 5- to 6-fold higher than those in control mice. Ultrastructural studies of glucagon- and MCA-treated tumors revealed the predominance of acinar-cystoid and secretory types of tumors, with the occurrence of large and dense secretory granules (Zymogen-like granules), markedly dilated endoplasmic reticulum cisternae, and lysosomes compared to only typical squamous neoplastic cells observed in MCA-treated mice. Scanning electron microscopic observations also indicated that neoplastic cells of MCA and glucagon-treated tumors exhibited characteristic secretory features on their cell surfaces (a marked increase in blebs and microvilli). These findings demonstrate that glucagon in pharmacological doses significantly enhanced the carcinogenic process and changed the cytodifferentiation of neoplastic cells and, thus, plays an important role in controlling tumor cell biology and neoplastic transformation.