TRANSGLUTAMINASE IN AZOXYMETHANE-INDUCED COLON-CANCER IN THE RAT

A widespread form of transglutaminase, tissue transglutaminase, has be en identified in a number of mammalian cell types, both normal and tra nsformed cells; its biological role is not well understood. We investi gated the effect of experimentally induced colon cancer on transglutam inase activity in the rat. Azoxymethane (15 mg/kg for six weeks), give n by a course of weekly intraperitoneal injections, produces tumors al most exclusively confined to the intestinal tract. Transglutaminase ac tivity was assayed on tissue homogenates both during the period of tre atment and, when the cancer had developed, on tumor tissue and on macr oscopically uninjured adjacent tissue. A transient proliferative phase was present in the intestine during azoxymethane treatment: in this p hase we found a coincidentally increased transglutaminase levels. Tran sglutaminase activity in tumors of both small and large intestine was significantly higher than in adjacent tissue. Immunohistochemistry rev ealed higher levels of transglutaminase in tumors, mainly localized in the extracellular matrix, than in adjacent tissues, where it was wide ly distributed. The present study shows that transglutaminase, besides its potential role in intracellular process during early proliferativ e phase of carcinogenesis, may also play an important role in matrix p rocessing during tumor growth and differentiation.