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https://hdl.handle.net/2440/14518
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dc.contributor.author | Crott, J. | - |
dc.contributor.author | Fenech, M. | - |
dc.date.issued | 2001 | - |
dc.identifier.citation | Mutagenesis, 2001; 16(3):213-217 | - |
dc.identifier.issn | 0267-8357 | - |
dc.identifier.issn | 1464-3804 | - |
dc.identifier.uri | http://hdl.handle.net/2440/14518 | - |
dc.description.abstract | Homocysteine (Hcy), an immediate precursor of methionine (Met), is considered a risk factor for cardiovascular disease, Alzheimer's disease and neural tube defects. Hcy concentration is also reported to correlate positively with the micronucleus index in lymphocytes in vivo, a marker of chromosome damage. However, it is unclear whether Hcy is genotoxic or simply a biomarker of folate deficiency, a known cause of chromosome damage. We investigated whether high concentrations of Hcy are genotoxic to human lymphocytes in vitro using the cytokinesis-block micronucleus assay. Eighteen lymphocyte cultures were initiated in Met-free and serum-free RPMI 1640 medium for each of four male volunteers aged 22-23 years. At 0, 24, 44 and 72 h, cultures were spiked with L-Hcy or L-Met to achieve concentrations ranging between 50 and 400 microM. The concentration of Hcy at 96 h ranged from 19.45 +/- 2.34 to 149.02 +/- 28.16 microM in Hcy cultures and 0.91 +/- 0.17 to 2.15 +/- 0.9 microM in Met cultures spiked with 50 and 400 microM of metabolite, respectively. Forty-four hours after mitogen stimulation, cytokinesis was inhibited with cytochalasin B. After 96 h, cells were transferred to microscope slides and the frequency of micronucleated-binucleate and necrotic cells was scored. Neither Hcy (P = 0.24) nor Met (P = 0.93) had an apparent dose effect on micronucleus frequency. However, when data were pooled, micronucleus frequency was moderately higher (50.1%) in Hcy- than in Met-spiked cultures (P = 0.04; paired t-test). Hcy concentration was positively correlated with necrosis (P < 0.0005; r(2)= 0.276), however, when data were pooled, levels of necrosis were higher in Met- than in Hcy-spiked cultures (P= 0.01; paired t-test). Further research is required to define more clearly the genotoxic and cytotoxic potential of homocysteine and its metabolites. | - |
dc.description.statementofresponsibility | Crott, Jimmy ; Fenech, Michael | - |
dc.language.iso | en | - |
dc.publisher | Oxford Univ Press | - |
dc.source.uri | http://dx.doi.org/10.1093/mutage/16.3.213 | - |
dc.subject | Lymphocytes | - |
dc.subject | Cells, Cultured | - |
dc.subject | Humans | - |
dc.subject | Necrosis | - |
dc.subject | Cytochalasin B | - |
dc.subject | Methionine | - |
dc.subject | Homocysteine | - |
dc.subject | Mutagens | - |
dc.subject | Analysis of Variance | - |
dc.subject | Micronucleus Tests | - |
dc.subject | Dose-Response Relationship, Drug | - |
dc.subject | Models, Chemical | - |
dc.subject | Time Factors | - |
dc.subject | Adult | - |
dc.subject | Male | - |
dc.title | Preliminary study of the genotoxic potential of homocysteine in human lymphocytes in vitro | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1093/mutage/16.3.213 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Fenech, M. [0000-0002-8466-0991] | - |
Appears in Collections: | Aurora harvest 7 Pharmacology publications |
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