Cancer Letters 91 (1995) 241-245 Melatonin enhances juncti0na.j transfer in normal C3H/lOT1/2 cells * Alejandro Ubeda*“, M. Angeles Trillo”, Dennis E. Howeb, Carl F. Blackman’ “Hospital Ram& y Cajai, Department de Investigacidn, 28034 Madrid, Spain bUS Environmental Protection Agency, Heahh Effects Research Laboratory (MD-68), Reseurch Triangle Park, NC 2771 I. C/SA Received 17January 1995; accepted 23 February 1995 Abstract Gap junctional intercellular communication is known to be involved in controlling cell proliferation and differentia- tion, and seems to play a crucial role in suppressionof tumor promotion. The pineal gland and its hormone, melatonin, are believed to intervene in the control of neoplastic processes. Several possible mechanismshave been su ted to be potentially responsible for melatonin’s oncostatic action; however, the actual mechanismsinvolved in melatonin’s effectsat the cellular level remain unidentified. In the present study low-density cultures of C3WlOT1/2 mome embryo fibroblasts were incubated until relatively quiescent monolayers were established(17- 18days). Gap jxmctianal intercel- lular communication in control samplesand in cells treated with lo-‘* to lo-’ M melatonin was determined by the scrape-loading assay using the fluorescent dye Lucifer yellow. The results showed that concentrations of mehttonin considered physiological (lo-” and IO-” M) induced a significant increase in the transfer of the dye to adjacent cells through gap junctions; both higher and lower concentrations were ineffective. These results suggestthat mektonin could exert its putative oncostatic action, in part, by modulating the levels of gap junctional intercellular communi- cation Keywords: Melatonin; Oncostatic; Dye transfer; Intercellular communication; Gap junctions * The research described in this article has been reviewed by the Health Effects Research Laboratory, US EPA, and is approved for publication.Approval does not signify that the contents necessarilyreflect the views and policies of the Agen- cy, nor does mentionof trade names or commercial products constitutes endorsement or recommendation for use. 1. InlToduction There is mounting evidence that the pineal gland and its hormone. melatonin. have a role in the con- *Correspondingauthor, Tel.: +34 1 7293475; Fax: +34 1 3581275; Email: Alejandro.Ubeda@hrc.es. trol of neopkkc processes.Abnormal levels of circulating melatonin have been found to be associated with malignant melanoma, breast 0304-3835/95/$09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3835(95)03736-G