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Biochemical Changes in Premalignant Intestines¹

Laboratory of Cell Metabolism, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The immunological properties of thymidine kinase from a variety of human tumors suggest that the form of the tumor enzyme resembles that found in the placenta and in the nondividing colonic flat mucosa. To examine the placenta-like characteristics of tumor thymidine kinase, the jejunum and colon from rats ranging in age from fetal to old and from animals treated with dimethylhydrzine (DMH), an intestinal carcinogen, have been studied. In normal jejunum, thymidine kinase activity decreased rapidly with age. Both the activity and the response to phospholipase C and to mercaptans in DMH-induced tumors resembled that of fetal gut, while those in abnormal appearing DMH-treated jejunum were intermediate between normal control of the same age and tumor. Similar but less pronounced changes were seen in the colon. In the jejunum, the level of another enzyme normally associated with rapid cell division, ornithine decarboxylase, was found to be over 100 times that of the liver, colon, and stomach. Treatment of the animals with acetylaminofluorene and with DMH resulted in elevated levels of the enzyme in liver and in colon, respectively, but had little effect on this enzyme in other tissues. The data presented indicate that there were premalignant changes in the levels of both of these enzymes in target tissues of animals treated with carcinogens.

¹ Presented at the Symposium "Cancer and Chemistry" as part of the Fourth Conference on Embryonic and Fetal Antigens in Cancer, November 2 to 5, 1975, Charleston, S. C. This investigation was supported by USPHS CA-14906 from the National Cancer Institute through the National Large Bowel Cancer Project, and by USPHS Grant CA-08748.

² Post Doctoral Fellowship 5 F 22 CA-01332. Present address: Department of Pharmacology, Baylor College of Medicine, Texas Medical Center, Houston, Texas.

³ Presenter.