ATYPICAL ASSOCIATION OF H-1 AND H-2 HISTAMINE-RECEPTORS WITH SIGNAL-TRANSDUCTION PATHWAYS DURING MULTISTAGE MOUSE SKIN CARCINOGENESIS

Objective: In the present work we studied the association of histamine receptors with second messengers during multistage carcinogenesis in Sencar mice skin. Methods: 96 Sencar female mouse, divided into six gr oups were used. Tumors appeared only in the 7,12-dimethylbenz[a]anthra cene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted group . Control groups received only TPA, or acetone or no treatment at all. Periodically during the promotion period, cAMP and inositol phosphate production were measured after stimulation with H-1 or H-2 agonists i n samples from all groups. Results: In non-treated skin, H-1 receptors were coupled to phosphatidylinositol hydrolysis and H-2 receptors med iated cAMP production. Conversely, in tumors H-2 receptors were associ ated with phosphatidylinositol hydrolysis and HI mediated a rise in cA MP levels. The skin among tumors and the skin from all control groups maintained the same coupling as non-treated skin. An increase in mast cell number, with a homogeneous subepithelial distribution and marked phenotypic changes, was also observed in promoted skin. Conclusions: T hese findings indicate an atypical association of histamine receptors with second messengers that could be a critical feature for the postul ated action of histamine in tumor growth.