STIMULATION OF INVIVO TUMOR-GROWTH AND PHORBOL ESTER-INDUCED INFLAMMATION BY N,N-DIETHYL-2-[4-(PHENYLMETHYL)PHENOXY] ETHANAMINE HCL, A POTENT LIGAND FOR INTRACELLULAR HISTAMINE-RECEPTORS

We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA 2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth. © 1991.