PMID- 9464620
OWN - NLM
STAT- MEDLINE
DCOM- 19980312
LR  - 20191024
IS  - 0960-8931 (Print)
IS  - 0960-8931 (Linking)
VI  - 7
IP  - 6
DP  - 1997 Dec
TI  - Selective incorporation of the prototype melanoma seeker thiourea into nascent 
      melanin: a chemical insight.
PG  - 478-85
AB  - The mechanism of selective incorporation of thiourea into melanotic melanoma was 
      investigated by model experiments in which the effect of the compound was 
      examined at various stages of melanogenesis in vitro. Up to 50% inhibition of 
      dopachrome formation was observed in the tyrosinase-dopa reaction in the presence 
      of thiourea at a 2:1 molar ratio with respect to the substrate. Under these 
      conditions, a major product was formed which was isolated and identified as a 1:1 
      dopa-thiourea adduct (adduct I). Subsequent stages of the oxidation were 
      characterized by the development of a yellow chromophore (lambdamax 440-460nm), 
      virtually identical to that obtained by separate oxidation of the adduct I. A 
      less remarkable effect of thiourea was observed on the oxidative polymerization 
      of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) 
      which was apparent on spectrophotometric and high pressure liquid chromatography 
      (HPLC) analysis. Radiolabelling experiments with 14C-thiourea showed that the 
      label was initially incorporated into the adduct I, while in the subsequent 
      stages of the oxidation it was associated with pigmented materials which escaped 
      direct analysis. Incorporation of labelled thiourea into dopa-melanins was found 
      to be significantly higher than incorporation into synthetic pigments from indole 
      precursors. These results provide a chemical basis for the interpretation of the 
      selective accumulation of thiourea in those melanoma areas with high rates of 
      melanin synthesis seen in autoradiographic experiments.
FAU - Palumbo, A
AU  - Palumbo A
AD  - Biochemistry Department, Zoological Station, Villa Comunale, Naples, Italy.
FAU - Mars, U
AU  - Mars U
FAU - De Martino, L
AU  - De Martino L
FAU - d'Ischia, M
AU  - d'Ischia M
FAU - Napolitano, A
AU  - Napolitano A
FAU - Larsson, B S
AU  - Larsson BS
FAU - Prota, G
AU  - Prota G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Melanoma Res
JT  - Melanoma research
JID - 9109623
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Melanins)
RN  - 63-84-3 (Dihydroxyphenylalanine)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
RN  - GYV9AM2QAG (Thiourea)
SB  - IM
MH  - Antineoplastic Agents/metabolism/*pharmacokinetics
MH  - Chemistry, Pharmaceutical
MH  - Dihydroxyphenylalanine/metabolism
MH  - Melanins/biosynthesis/*metabolism
MH  - Melanoma/*drug therapy/*metabolism
MH  - Monophenol Monooxygenase/metabolism
MH  - Oxidation-Reduction
MH  - Spectrophotometry, Ultraviolet
MH  - Structure-Activity Relationship
MH  - Thiourea/chemistry/metabolism/*pharmacokinetics
EDAT- 1998/02/17 00:00
MHDA- 1998/02/17 00:01
CRDT- 1998/02/17 00:00
PHST- 1998/02/17 00:00 [pubmed]
PHST- 1998/02/17 00:01 [medline]
PHST- 1998/02/17 00:00 [entrez]
AID - 10.1097/00008390-199712000-00006 [doi]
PST - ppublish
SO  - Melanoma Res. 1997 Dec;7(6):478-85. doi: 10.1097/00008390-199712000-00006.