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Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cyntia 4 I-80126, Naples Italy.
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Via Cyntia 4 I-80126, Naples Italy.
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2010 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 411, no 17-18, 1195-1203 p.Article in journal (Refereed) Published
Abstract [en]

Currently used as structural markers for pheomelanin identification and quantitation, benzothiazole compounds derived from isomeric cysteinyldopas have been indicated by recent in vitro studies as new potential pheomelanogenesis intermediates. Prompted by previous reports on the occurrence of large amounts of 5-S-cysteinyldopa (5-S-CD) and trichochromes in urine of patient with diffuse melanosis of melanoma we investigated the presence of benzothiazole compounds in the urine of these patients.

Hydrophilic interaction liquid chromatography on zwitterionic stationary phase (ZIC-HILIC) and photo-diode array (PDA) detection was used for analysis of 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-5), and 7-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-2), derived from 5-S-CD and 2-S-cysteinyldopa (2-S-CD) isomers, respectively. Isocratic mobile phase with minimal sample preparation allowed efficient separation of the compounds, which were safely identified by their typical absorption features.

Among 21 melanoma patients examined three showed diffuse melanosis. The levels of urinary BTCAs were found to be highly associated with melanosis but more loosely to excreted 5-S-CD. Analysis of the pigmented fraction of urine following alkaline hydrogen peroxide degradation and quantitation of BTCAs provided evidence for the presence of pheomelanins at higher levels in patients with melanosis.

Place, publisher, year, edition, pages
lsevier Science B.V., Amsterdam , 2010. Vol. 411, no 17-18, 1195-1203 p.
Keyword [en]
Benzothiazole, benzothiazole-2-carboxylic acids, diffuse melanosis, melanoma, HILIC, pheomelanin, BTCA
National Category
Other Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-21817DOI: 10.1016/j.cca.2010.04.019ISI: 000280033400005OAI: oai:DiVA.org:liu-21817DiVA: diva2:241760
Available from: 2009-10-05 Created: 2009-10-05 Last updated: 2010-08-11Bibliographically approved
In thesis
1. Pheomelanin markers in melanoma with reference to their excretion into urine
Open this publication in new window or tab >>Pheomelanin markers in melanoma with reference to their excretion into urine
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Skin pigmentation is an important issue in most cultures. Until recently we have not understood the most important elements of pigmentation regarding detailed chemical structure. The synthesis of melanin is very complex, and although core enzymes, other important proteins, and parts of the melanin structure have been identified much information in this context awaits disclosure.

The function of the melanocyte and the deposition of melanin pigments into the keratinocytes are very important in the protection against UV light. Melanin pigments consist of high-molecular structures often described as brown to black eumelanin and yellow to red pheomelanin. Eumelanin is photoprotective, whereas pheomelanin is believed to be carcinogenic after UV radiation. There is strong evidence that people of fair complexion with freckles who tan poorly are at higher risk of developing melanoma. These people have a higher pheomelanin to eumelanin ratio in their skin.

Melanoma, one of the most widely spread cancers, is derived from melanocytes. There is accumulating evidence that pigment constitution is highly involved in the development of melanoma. We found that patients with advanced melanoma secrete substantial amounts of pigment structures into the urine, in particular those with diffuse melanosis. In subsequently performed experiments we purified these pigments and subjected the product to chemical degradation by either hydrogen peroxide oxidation or hydriodic hydrolysis. Several new chromatographic methods were developed for the structural analysis of these products. Structural analysis of new chromatographic peaks was performed. In conclusion, complex pheomelanin structures as well as low molecular weight pigments and free benzothiazoles have been identified in the urine of patients with melanoma and diffuse melanosis.

The present thesis provides new insight into melanogenesis and melanoma progression. This opens the doorway to further approaches to the investigation of melanins and can help to understand fundamental problems about the structure and biosynthesis of natural melanins.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 67 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1143
Keyword
Pheomelanin, melanoma, benzothiazole, aminohydroxyphenylalanine, diffuse melanosis, HILIC
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-21486 (URN)978-91-7393-566-1 (ISBN)
Public defence
2009-10-23, Berzeliussalen, Hälsouniversitet, Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)
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Available from: 2009-10-12 Created: 2009-10-02 Last updated: 2010-01-14Bibliographically approved

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Nezirevic Dernroth, DzenetaÅrstrand, KerstinKågedal, Bertil

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