Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria (AIP) and lead poisoning, undergoes metal-catalyzed oxidation in air-equilibrated solutions buffered at neutral pH, yielding free radicals (O2, HO. and ALA.). The capacity of ALA to release iron from horse spleen and rat liver ferritin in vitro and to concomitantly initiate liposome lipid peroxidation was characterized. ALA induced iron release from ferritin in normally aerated solutions, in a dose (0.05-1 mM)- and time (0-120 min)-dependent manner; no reaction occurs under nitrogen. Superoxide dismutase partially inhibited (50% at 100 U/ml) iron release by 0.5 mM ALA, whereas the addition of catalase (50 U/ml) had no effect under these conditions. In phosphatidylcholine: cardiolipin (80:20) liposomes, and in the presence of 2 microM EDTA, ALA (0.025-1 mM) per se had a subtle effect on lipid peroxidation, while after addition of ferritin (0.25 mg/ml) there was a significant increase in lipid peroxidation as evaluated by dose-dependent formation of 2-thiobarbituric-reactive substances and diene conjugation. In vivo, iron accumulation in the liver of ALA-treated rats was observed. Altogether, these data demonstrate the ability of ALA-generated free radicals to release iron from ferritin and to affect iron metabolism in vivo. ALA-mediated iron release from ferritin, therefore, may aggravate oxidative damage to cell components and contribute to the pathology observed in AIP (eg., primary liver cancer) and lead poisoning.
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PMID:5-Aminolevulinic acid induces iron release from ferritin. 784 Jun 72

5-Aminolevulinic acid (ALA) is a heme precursor, pathological accumulation of which is associated with liver cancer. We show that the reactive oxygen species produced upon ALA metal-catalyzed oxidation promote the formation of several radical-induced base degradation products in isolated DNA. The distribution of modified bases is similar to that obtained upon gamma irradiation. This observation strongly suggests the involvement of hydroxyl radicals in the ALA-mediated DNA damage. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 5-hydroxy-2'-deoxycytidine in organ DNA of rats chronically treated with ALA were observed. This is strongly suggestive of the implication of hydroxyl radicals in the ALA-induced degradation of cellular DNA.
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PMID:Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA bases by 5-aminolevulinic acid. 964 83

5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in lead poisoning and inborn porphyrias. It has been shown to produce reactive oxygen species upon metal-catalyzed aerobic oxidation and to cause oxidative damage to proteins, liposomes, DNA, and subcellular structures. Studies have also shown that ALA may condense to yield the cyclic product 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY). Here we propose that DHPY could be involved in DNA damage in the presence of high concentrations of ALA. Exposure of plasmid pUC19 DNA to low concentrations of DHPY (2-10 microM) in the presence of 0.1 mM Cu2+ ions causes DNA strand breaks, as demonstrated by agarose gel electrophoresis. It was also shown that in the presence of Cu2+ ions DHPY is able to increase the oxidation of monomeric 2'-deoxyguanosine to form 8-oxo-7,8-dihydro-2'-deoxyguanosine as inferred from high performance liquid chromatography measurements using electrochemical detection. Addition of a metal chelator (bathocuproine, 0.5 mM), the DNA compacting polyamines spermidine (1 mM) and spermine (1 mM) or antioxidant enzymes such as superoxide dismutase (10 microg/ml) and catalase (20 pg/ml) protect the DNA against these damages. The data presented here are discussed with respect to the increased frequency of liver cancer in patients with acute intermittent porphyria.
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PMID:DNA damage by 3,6-dihydropyrazine-2,5-dipropanoic acid, the cyclic dimerization product of 5-aminolevulinic acid. 1150 55

The possibility of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) for liver cancer was investigated using a chemically induced hepatocellular carcinoma (HCC) model. Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT. We determined the fluorescence intensity of PpIX in HCC and nontumoral tissue in the liver. 5-Aminolaevulinic acid was intravenously injected to male Fisher rats with HCC at a dose of 500 mg x kg(-1), and the fluorescence intensity in each tissue sample excised from liver was measured with a spectrofluorometer at 1, 3 and 6 h after administration. Fluorescence intensity was at a peak of 3 h after administration in both HCC and nontumoral tissue. The accumulation of PpIX in HCC was higher than that in the nontumoral tissue at 1 h (P<0.001) and 3 h (P<0.05) after ALA administration. Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour. Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC. These findings suggest the possibility to detect HCC by fluorescence and to treat HCC by light.
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PMID:Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma. 1291 87