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|Title:||Preliminary study of the genotoxic potential of homocysteine in human lymphocytes in vitro|
|Citation:||Mutagenesis, 2001; 16(3):213-217|
|Publisher:||Oxford Univ Press|
|Crott, Jimmy ; Fenech, Michael|
|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.|
|Keywords:||Lymphocytes; Cells, Cultured; Humans; Necrosis; Cytochalasin B; Methionine; Homocysteine; Mutagens; Analysis of Variance; Micronucleus Tests; Dose-Response Relationship, Drug; Models, Chemical; Time Factors; Adult; Male|
|Appears in Collections:||Pharmacology publications|
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