Human Melanocyte Biology, Toxicology, and Pathology

The human melanocytes of the skin, hair, eyes, inner ears, and covering of the brain provide physiologic functions important in organ development and maintenance. Melanocytes develop from embryonic neural crest progenitors and share certain traits with other neural crest derivatives found in the adrenal medulla and peripheral nervous system. The distinctive metabolic feature of melanocytes is the synthesis of melanin pigments from tyrosine and cysteine precursors involving over 100 gene products. These complex biochemical mechanisms create inherent liabilities for melanocytic cells if intracellular systems necessary for compartmentalization, detoxification, or repair are compromised. Melanocyte disorders may involve pigmentation, sensory functions, autoimmunity, or malignancy. Environmental factors such as ultraviolet radiation and chemical exposures, combined with heritable traits, represent the principal hazards associated with melanocyte disorders.

Key words:

• Melanocytes
• Melanin
• Melanoma
• Ocular toxicity
• Ototoxicity
• Oxidative stress

Acknowledgments

This article is not an official guidance or policy statement of U.S. Food and Drug Administration (FDA). No official support or endorsement by the U.S. FDA is intended or should be inferred.

Notes

^a Adapted from Liu et al. [96].

^b Isolated using enzymatic method.

^c Range of values from three hair samples.

^d Sum of total amino acids from HCl hydrolysis.

^e Soluene 350 extract, A ₅₀₀× 1000.

^f PTCA (pyrrole-2,3,5-tricarboxylic acid) generated from eumelanin with H₂O₂/OH⁻.

^g AHP (aminohydroxyphenylalanine) formed from pheomelanin by Hl-hydrolysis.

^a Compiled from reviews by Njoo and Westerhof (Am. J. Clin. Dermatol. 2001;2:167–181) and Boissy and Manga (Pigm. Cell Res. 2004;17:208–214).

^a Compiled from Boissy and Manga (Pigm. Cell Res. 2004, 17: 208–214).