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Polyethylene-Glycol-mediated Delivery of Liposome-entrapped Pigments into Fibroblasts: Experimental Pigment Cells as Models for Mutator Phenotypes¹

Division of Dermatology and Cutaneous Sciences [S. S., K. J.], Department of Pharmacology [T. M. A.], Faculty of Medicine, University of Alberto, Edmonton, T6G 2S2, Alberta, Canada

² To whom requests for reprints should be addressed, at Dermatology & Cutaneous Sciences, Department of Medicine, 260G Heritage Medical Research Centre, University of Alberta, T6G 2S2, Canada.

The role of epidermal melanin pigments in the development of skin cancer remains unclear. A new technique for the specific introduction of compartmentalized melanin into nonpigmented human fibroblasts through the use of liposomes and polyethylene glycol (PEG) is presented. The delivery of liposome-encapsulated material to cells was characterized by: (a) high efficiency of delivery through PEG-mediated endocytosis at 37°C; (b) intracellular acidification of liposome entrapped pH-sensitive 8-hydroxypyrene-3,6,8-trisulfonic acid after delivery; (c) similar incorporation and acidification of apolipoprotein E-associated liposomes into fibroblasts via the low-density lipoprotein-receptor pathway; and (d) discharge into the extracellular space after incorporation. Similar experiments were carried out with melanin-containing liposomes that were used to introduce compartmentalized melanin into fibroblasts, through PEG-mediated delivery. These "artificial" melanocytes had functional analogies to genuine melanocytes in that (a) in both cell types melanin compartmentalization was at a lower pH; and (b) liposome contents were later expelled in analogy to the putative biological process of melanin expulsion from the melanocyte. The modified fibroblasts provided potential "mutator" phenotypes with specific melanin pigmentation, and established a new basis for studying the role of melanin pigmentation in cancer development.

¹ This work was supported in part by grants from the National Cancer Institute of Canada, Medical Research Council of Canada (MA-9127: MT-10264), Alberta Cancer Board, and Alberta Heritage Foundation for Medical Research.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/ 1/92. Accepted 9/24/92.