EFFECTS OF HISTAMINE, H-1, H-2 AND H-IC RECEPTOR ANTAGONISTS AND ALPHA-FLUOROMETHYLHISTIDINE ON THE GROWTH OF HUMAN COLORECTAL-CANCER IN THE SUBRENAL CAPSULE ASSAY

Biogenic amines play an important role in regulating cell proliferatio n in the normal and neoplastic colon. Elevated histidine decarboxylase (HDC) activity has been measured in human colorectal tumors. H-2 anta gonists can suppress the growth of colorectal cancer and their inclusi on in human therapy has been proposed. We studied the effects of hista mine, cimetidine, mepyramine and alpha-fluoromethylhistidine (FMH) on the growth of colorectal tumors in ten patients in the 6-day mouse sub renal capsule assay (SRCA). The effect of the H-ic antagonist DPPE was tested in two assays. In summary, a reduction of tumor size was achie ved with histamine and DPPE. In addition, significant inhibition of tu mor growth was seen in the FMH-treated animals. When pooled by their g rowth potential, as assessed by the growth of saline-treated controls, FMH and DPPE caused distinct tumor reduction in rapidly growing tumor s. In the moderately growing tumors, histamine and mepyramine were the most effective.