Selective cytotoxicity of N-acetyl-4-S-cysteaminylphenol on follicular melanocytes of black mice.
Previous in vivo studies have shown that 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) have antimelanoma effects and that N-Ac-4-S-CAP produced a 98% depigmentation of hair follicles of black mice. This study investigated the process of selective melanocytotoxicity by N-Ac-4-S-CAP through light and electron microscopy studies of hair follicles obtained from newborn black mice treated with N-Ac-4-S-CAP. Visible changes in follicular melanocytes were found 4 h after intraperitoneal (i.p.) administration. Clumps of melanin granules and areas of melanocytic nuclear condensation were seen in the hair follicles. On electron microscopy there was progressive destruction of melanocytes with swelling of membranous organelles, nuclear condensation, and vacuolation of the cytoplasm, culminating in completely necrotic cells. None of these changes were demonstrated in the surrounding keratinocytes. N-Ac-4-S-CAP appears to have specific, cytotoxic effects on melanocytes actively producing eumelanin. The drug may not affect precursor or dormant melanocytes which retain the ability to become active, melanin-producing cells.
Wong
M
M
Division of Dermatology and Cutaneous Sciences, University of Alberta, Heritage Medical Research Centre, Edmonton, Canada.
Jimbow
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D003543:Cysteamine / Q000633:toxicity* / Q000031:analogs & derivatives; D006197:Hair / Q000187:drug effects* / Q000648:ultrastructure; D008544:Melanocytes / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010636:Phenols / Q000633:toxicity*; D010858:Pigmentation / Q000187:drug effects*
D000970:Antineoplastic Agents; D010636:Phenols; D003543:Cysteamine; C066420:N-acetyl-4-S-cysteaminylphenol; C043037:4-S-cysteaminylphenol