Interaction of Several Mono- and Dihydroxybenzene Derivatives of Various Depigmenting Potencies with L-3,4-Dihydroxyphenylalanine-Melanin

Details

• Personal Author:
  Menter JM ; Willis I
• Description:
  Certain mono- and dihydroxybenzene derivatives cause depigmentation of skin and hair, and appear to be selectively cytotoxic for melanized pigment cells. As direct physical and/or chemical interaction between depigmenter (DP) and pigment melanin may play a role in depigmentation, we have carried out preliminary studies in model systems where such interactions may easily be separated from effects due to tyrosinase, melanosomal proteins, and other components. We have used synthetic L-3,4-hydroxyphenylalanine (L-DOPA)-melanin as a protein-free model pigment and potassium ferricyanide as a model electron acceptor. Compounds studied were catechol, 4-t-butylcatechol, 4-methylcatechol, 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid, hydroquinone, 4-methoxyphenol, 4-t-butylphenol, and 2,6, di-t-butyl-4-methylphenol (BHT) in 0.1 M phosphate buffer, pH 7.4. These compounds vary widely in their ability to depigment hair and skin. Ferricyanide reduction by DP in the presence and absence of melanin was monitored spectrophotometrically. The sparingly soluble BHT and 4-t-butylphenol did not reduce ferricyanide in the absence or presence of melanin. For the other compounds, kinetic analysis demonstrated direct interaction between each DP and melanin. Except for dihydroxyphenylacetic acid, reduction kinetics were consistent with a mechanism involving noninteractive binding of both DP and ferricyanide to melanin prior to coupled electron transfer through the melanin backbone. Kinetic analysis afforded KB, a thermodynamic constant (M-1) for DP-melanin binding, and k', a rate parameter (M s-1) for electron transfer. A dimensionless enhancement factor (EF) was defined as k'KB/ks, with ks a pseudo-first-order constant (s-1) for ferricyanide reduction in the absence of melanin. Depending on the reductant, melanin either retards (EF < 1) or accelerates (EF > 1) the rate of ferricyanide reduction. There appears to be a direct relationship between EF and depigmenting potency. There is no relationship between depigmenting power and the ability per se of the DP to bind to melanin or to reduce ferricyanide. [Description provided by NIOSH]
• Subjects:
  Benzene Cytotoxins Enzymes Occupational Health Safety
• Keywords:
  Benzenes Cytotoxic Effects Cytotoxicity Enzyme Activity Pigmentation Pigmentation Disorders
• ISSN:
  0003-9861
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Georgia ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  244
• Issue:
  2
• NIOSHTIC Number:
  nn:20060329
• Citation:
  Arch Biochem Biophys 1984 Feb; 244(2):846-856
• Contact Point Address:
  Julian M. Menter, Division of Dermatology, Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia 30310-1495 USA
• Federal Fiscal Year:
  1986
• Performing Organization:
  Morehouse School of Medicine, Atlanta, Georgia
• Peer Reviewed:
  True
• Start Date:
  19820929
• Source Full Name:
  Archives of Biochemistry and Biophysics
• End Date:
  19860331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9bc0cbc3d86b17077b5a797e26b968c5b0256713d0b364f74ba33b7e9fde55542dbebda4ee14f8f08ca440dd32dba3bcc1b398a9ad07aa3f6fe4b483377c1115
• Download URL:
  https://stacks.cdc.gov/view/cdc/224271/cdc_224271_DS1.pdf
• File Type:
  [PDF - 763.07 KB ]