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Analytical, ultrastructural, autoradiographic and biochemical studies on [ 3 H]dicarboxylic acid added to cultures of melanoma cells
Author(s) -
WARD B. J.,
BREATHNACH A. S.,
ROBINS E. J.,
BHASIN Y.,
ETHRIDGE L.,
PASSI S.,
NAZZAROPORRO M.
Publication year - 1984
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.1984.tb04013.x
Subject(s) - endoplasmic reticulum , golgi apparatus , tyrosinase , mitochondrion , lentigo maligna , biochemistry , dicarboxylic acid , biology , vesicle , intracellular , melanosome , microbiology and biotechnology , chemistry , enzyme , melanin , melanoma , membrane , cancer research
SUMMARY Lentigo maligna and malignant melanoma can be treated by dicarboxylic acids (C 9 and C 12 , which are competitive inhibitors of tyrosinase. We therefore studied the intracellular location and possible sites of action of dodecanedioic acid (C 12 ) in murine melanoma cells, using EM autoradiography and biochemical analysis of lipid extracts by HPLC. Significant levels of radioactivity were found in the mitochondria and in the nuclei but not in association with membranes of rough endoplasmic reticulum, Golgi‐associated endoplasmic reticulum, or Golgi apparatus, and not in coated vesicles or melanosomes. Biochemical analysis revealed that the diacid underwent β‐oxidation, which occurs only in mitochondria. The results suggest that the toxicity of dicarboxylic acids in melanoma cells is not related to anti‐tyrosinase activity but may be due to interference with oxidoreductase enzymes in the mitochondria and possibly to inhibition of DNA synthesis in the nucleus.