Deletions in the mitochondrial DNA and decrease in the oxidative phosphorylation activity of children with Fanconi syndrome secondary to antiblastic therapy.
The aim of this study is to verify whether there are deletions in mitochondrial DNA (mtDNA) and disorders in oxidative phosphorylation (Ox-phos) complexes in the pathogenesis of secondary Fanconi syndrome (FS). We studied 18 children with tumors who were previously treated with chemotherapy and were off therapy for at least 1 year. All the children had normal renal function at diagnosis. Only 4 children received ifosfamide (IFO) and platinum compounds. We evaluated renal function, Ox-phos activity measured on platelets, and mtDNA extracted from platelets for all patients. Only 2 patients, both treated with IFO and carboplatinum (CARBO) for Wilms' tumor and germ-cell tumor, respectively, developed FS 1 and 3 years after termination of therapy. They had decreased activities of Ox-phos that were statistically significant only for nicotinamide adenine dinucleotide (NAD)-reduced cytochrome-c reductase and cytochrome-c oxidase and specific and unidentified deletions in mtDNA that were not maternally inherited. Our data suggest that treatment with IFO and CARBO might be responsible for deletions in mtDNA, decreased activity of Ox-phos, and impaired rates of transport of D-glucose, phosphate, and amino acids.
Departments of Pediatric Hematology-Oncology, Biochemistry, and Pediatrics, University of Catania, Italy.
A
A
Di Cataldo
M
M
Palumbo
D
D
Pittalà
M
M
Renis
G
G
Schilirò
A
A
Russo
R
R
Ragusa
F
F
Mollica
S
S
Li Volti
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D015139:Blotting, Southern; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D005198:Fanconi Syndrome / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D016133:Polymerase Chain Reaction
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004272:DNA, Mitochondrial; D016190:Carboplatin; D007069:Ifosfamide