PMID- 8068712
OWN - NLM
STAT- MEDLINE
DCOM- 19940929
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1200
IP  - 3
DP  - 1994 Aug 18
TI  - Specific incorporation of 2-thiouracil into biological melanins.
PG  - 271-6
AB  - 2-Thiouracil (TU), an antithyroid drug, is generally recognized as a highly 
      specific melanoma seeker owing to its capability of being selectively accumulated 
      into active melanin-producing tissues. We recently reported evidence that in 
      vitro TU is capable of reacting with dopaquinone (DQ), an early intermediate in 
      melanin biosynthesis, to give an addition product characterized as 
      6-S-thiouracildopa (TD). However, several aspects of the mechanism of the uptake 
      of TU into melanin in vivo still need to be clarified. We report here the 
      extremely rapid incorporation of [2-14C]thiouracil into melanoma tumors growing 
      subcutaneously in mice and show its selective accumulation into melanin by 
      isolation and purification of the pigment fraction. Formation of the TD adduct in 
      the tumor was examined by HPLC analysis of the soluble fractions of the tissue 
      homogenates: however, no trace of TD could be detected on account of its rapid 
      oxidation by the melanogenic enzyme tyrosinase, as evidenced by in vitro kinetic 
      measurements. Monitoring the course of the tyrosinase-catalyzed oxidation of 
      5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in 
      the presence of TU, at various molar ratios, provided evidence for the ability of 
      the drug to affect melanogenesis by interaction with biosynthetic intermediates 
      beyond the DQ stage, suggesting other possible modes for its chemical binding to 
      the growing pigment.
FAU - Palumbo, A
AU  - Palumbo A
AD  - Biochemistry Department, Zoological Station, Villa Comunale, Naples, Italy.
FAU - Napolitano, A
AU  - Napolitano A
FAU - De Martino, L
AU  - De Martino L
FAU - Vieira, W
AU  - Vieira W
FAU - Hearing, V J
AU  - Hearing VJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Melanins)
RN  - 59X161SCYL (Thiouracil)
SB  - IM
MH  - Animals
MH  - Carbon Radioisotopes
MH  - Female
MH  - Kinetics
MH  - Melanins/*metabolism
MH  - Melanoma, Experimental/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidation-Reduction
MH  - Thiouracil/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 1994/08/18 00:00
MHDA- 1994/08/18 00:01
CRDT- 1994/08/18 00:00
PHST- 1994/08/18 00:00 [pubmed]
PHST- 1994/08/18 00:01 [medline]
PHST- 1994/08/18 00:00 [entrez]
AID - 0304-4165(94)90167-8 [pii]
AID - 10.1016/0304-4165(94)90167-8 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1994 Aug 18;1200(3):271-6. doi: 
      10.1016/0304-4165(94)90167-8.