Stimulation of in vivo 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.
Department of Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
L J
LJ
Brandes
W A
WA
Beecroft
G R
GR
Hogg
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology*; D006965:Hyperplasia; D007249:Inflammation; D007940:Leukemia L5178 / Q000473:pathology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D008940:Mitotic Index / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology* / Q000633:toxicity
D006633:Histamine Antagonists; D010647:Phenyl Ethers; D011968:Receptors, Histamine; D015127:9,10-Dimethyl-1,2-benzanthracene; C043062:tesmilifene; D013755:Tetradecanoylphorbol Acetate