The cytotoxicity of gamma-L-glutaminyl-4-hydroxybenzene for cells that contain tyrosinase, a study of melanocytes in the hair follicle of the mouse.
The s.c. administration of gamma-L-glutaminyl-4-hydroxybenzene (GHB) to neonatal black mice produced a prompt, generalized, and selective swelling and lysis of the melanocytes of the hair follicles. The findings indicate that this cytotoxic effect was dependent upon the intracellular activation of GHB by tyrosinase. Supportive of this conclusion were: (a) an absence of comparable cytological alterations in adjacent keratinocytes; (b) a lack of response by melanocytes of albino mice; and (c) patterns of deficient pigmentation produced by GHB in juvenile black mice, suggesting that susceptible follicles were those in the tyrosinase-producing growth phase. The administration of GHB also induced condensation, or "apoptosis," of individual follicular keratinocytes of both black and albino mice and in the melanocytes in the latter. This response was apparently independent of tyrosinase. It was transitory and without appreciable effect on hair growth. The findings further characterize the selective cytolytic properties of GHB for mammalian cells that possess tyrosinase and suggest a potential for this natural compound as a chemotherapeutic agent against melanocarcinoma.
D000367:Age Factors; D000818:Animals; D004156:Catechol Oxidase / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives; D006197:Hair / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*; D010858:Pigmentation / Q000187:drug effects
D010636:Phenols; D005973:Glutamine; C001298:gamma-L-glutaminyl-4-hydroxybenzene; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase