Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether or not the mitochondrial genotypes affect radiation-induced micronucleus (MN) formation. For that purpose, the rho+, KT1 and rho0 human osteosarcoma cell lines were used, which carry the wild-type mitochondrial DNA (mtDNA), the tRNALys mutant mtDNA and no mtDNA, respectively. Despite no significant difference in the clonogenic radiosensitivity, the rho+, KT1 and rho0 cells exhibited high, intermediate and low radiosensitivities, respectively, to the MN induction in cytokinesis-blocked binucleated cells. Such differential MN inductions were correlated with high, intermediate and low levels of cellular ATP in the rho+, KT1 and rho0 cells, respectively, but not exactly with ROS production. Antimycin A that inhibits the respiratory complex III reduced the rate of radiation-induced MN induction in the rho+ and KT1, but not rho0 cells. Thus, the functional status of the mtDNA to produce ATP appears to play a significant role for radiation-induced MN.
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PMID:Mitochondrial genotypes and radiation-induced micronucleus formation in human osteosarcoma cells in vitro. 1129 90

Since de-novo synthesis of pyrimidine nucleotides is coupled to the mitochondrial respiratory chain (RC) via dehydroorotic acid dehydrogenase (DHODH), respiratory chain dysfunction should impair pyrimidine synthesis. To investigate this, we used specific RC inhibitors, Antimycin A and Rotenone, to treat primary human keratinocytes and 143B cells, a human osteosarcoma cell line, in culture. This resulted in severe impairment of de novo pyrimidine nucleotide synthesis. The effects of RC inhibition were not restricted to pyrimidine synthesis, but concerned purine nucleotides, too. While the total amount of purine nucleotides was not diminished, they were significantly broken down from triphosphates to monophosphates, reflecting impaired mitochondrial ATP regeneration. The effect of Rotenone was similar to that of Antimycin A. This was surprising since Rotenone inhibits complex I of the respiratory chain, which is upstream of ubiquinone where DHODH interacts with the RC. In order to avoid unspecific effects of Rotenone, we examined the consequences of a mitochondrial DNA mutation that causes a specific complex I defect. The effect was much less pronounced than with Rotenone, suggesting that complex I inhibiton cannot fully explain the marked effect of Rotenone on pyrimidine nucleotide synthesis.
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PMID:Severe impairment of nucleotide synthesis through inhibition of mitochondrial respiration. 1557 Dec 45