In Vivo Depigmentation by Hydroxybenzene Derivatives

Details

• Personal Author:
  Chapman W ; Etemadi AA ; Hollins TD ; Menter JM ; Willis I
• Description:
  Certain mono- and dlhydroxybenzene derivatives are selectively cytotoxic for melanocytes In vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxiclty/hair depigmentation in C57BI mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihy-droxyphenylalanlne (DOPA) or 3,4-dlhydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective Isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57BI mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 µM bovine serum albumin (BSA) In vitro varies widely, with tBCQ >> MMEHQ = DOPACQ > DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyroslnase-generated 1,2-quinones. This mechanism evidently differs from that involved In In vitro hydroxybenzene melanocytotoxlclty of melanoma cells, in which active oxygen Intermediates generated by hydroxybenzene autoxldatlon play a significant role. The most reliable prognosticator of In vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reactina with orotein -SH. [Description provided by NIOSH]
• Subjects:
  Animals Benzene Cytotoxins Enzymes Occupational Health Safety
• Keywords:
  Animal Studies Benzenes Cytotoxic Effects Cytotoxicity Enzyme Activity In Vivo Studies Pigmentation Pigmentation Disorders
• ISSN:
  0960-8931
• 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
• Pages in Document:
  443-449
• Volume:
  3
• Issue:
  6
• NIOSHTIC Number:
  nn:20058949
• Citation:
  Melanoma Res 1993 Dec; 3(6):443-449
• Contact Point Address:
  J. M. Menter, Department of Medicine, Morehouse School of Medicine, Atlanta, GA 30310, USA
• CAS Registry Number:
  Phenol (CAS RN 108-95-2)
• Federal Fiscal Year:
  1994
• Performing Organization:
  Morehouse School of Medicine, Atlanta, Georgia
• Peer Reviewed:
  False
• Start Date:
  19820929
• Source Full Name:
  Melanoma Research
• End Date:
  19860331
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85254af3e9a08fc6ee02008fd288dd2355f9c160b5a7b69957714fa5f16a796bb21b870e796bb19d375110e887b39ea0b754348ca071dc9f491e6f030723b818
• Download URL:
  https://stacks.cdc.gov/view/cdc/223300/cdc_223300_DS1.pdf
• File Type:
  [PDF - 276.41 KB ]