| Folic acid (FA) is an important micronutrient of the normal growth in the maintenance of the natural function of haematogenous system and in the prevention of the growthful defect and cardiovascular disease. There are two Pathways of FA metabolizing .(1) FA is required for the synthesis of S-adenosyl methionine via a series of metablism, the common methyl donor required for the maintenance of methylation patterns in DNA that determine gene expression and DNA conformation and that assure some high methylation on some chromosomes that is greatly important to normally separate during mitotic division. (2) FA is required for the synthyesis of dTMP from dUMP. Under conditions of FA deficiency, dUMP accumulates and as a result urail is incorporated into DNA instead of thy mine. And the conquence of DNA duplication and reparation , excessive incorporation of uracil in DNA not only result in point mutation ,but may also result in the generation of single- and double-stranded DNA breaks , chromosome breakage and of the activation of proto-oncogene.We study the effect of the cytotoxicity and genotoxicity in human lymphocyte in folic acid deficiency by the cytokinesis-block micronucleus assay from which we obtain a comprehensive information of the cytotoxicity and genotoxicity. The cytotoxic indexs include cell NDI, apoptosis and necrosis, and the genotoxic indexs involve binucleated micronucleus, nucleoplasmic bridges and nuclear buding by cytochalasin B blocking.There are two proportions in the our study. The first is the study of the cytotoxic and genotoxic effects induced by FA deficiency in breast cancer patient's lymphocytes with BRCA1 mutation. The second is the study of the cytotoxic and genotoxic effects induced by FA deficiency in human lymphocytes. First the study of the cytotoxic and genotoxic effects induced by FA deficiency in breast cancer patient's lymphocytes with BRCA1 mutation.There are two cell lines in the first, one is the breast cancer patient's lymphocytes line with BRCA1 mutation. The other is human lymphocyte line that is control group. The lymphocyte lines are cultured in RPMI-1640 medaim containing 6,12,60,120,240and 2260nM(normal RPMI-1640 medium) FA for nine days. And cultures is incubated at 37C and 5% CO2 in the humidified incubator. Medium is changed at days 3 and 6, cytokinesis is inhibited on day 8. Cytochalasin B is added to each tube(4.5ug/ml) and 28h later cells are harvested. Cells are centrifuged at 1000rpm for 10 minutes and dispart supernatant. Added 20ul foetal calf serum with 5% DMSO into cell deposit ,mixing and static culture at room temperature for 5 minutes. Spread cells on the cleaness slides ,which are air dried,fixed and stained with 5% Giemisa. Sample of 1000 binucleated cells are scored on every slide to determine frequency of Mned of binucleated cell, NPB and BUD. Sample of 500 cells to determine nuclear division index( NDI),and frequency of necrotic and apoptotic cells. The results suggest:1. the breast cancer patient's lymphocyte line with BRCAI mutation (GM13705)The effect of cytotoxicity: 1) The NDI expectancy of every FA concentration has no significance(p>0.05), which FA is not relate to the growth of GM13705. 2) Frequency of GM13705 apoptosis and necrosis are negative correlated to FA dose(rapoptosis=-0.706;rnecrosis=-0.472). They minimize when FA concentration is 240nM.The effect of genotoxicity: 1) Frequency of the binucleated MN at 6nM,12nM and 60nM FA concentration compared withthat of others is significant (p<0. 05). It suggests that frequency of the binucleated MN is minimum at 120nM FA concentration; 2) Frequency of NPB in lower FA dose is significant higher than that of 120 nM, 240 nM and 2260 nM, it is significant(p<0.05). It indicates that frequency of NPB is minimum at 120nM; 3) Frequency of bud falls with the growth of FA dose. 4)Three parameters above are strong positivecorrelated to each other(r=0. 764, P <0.001; r=0. 854, P (0.001; r=0. 837, P <0. 001) . MN, NPB and BUD of GM13705 is negative correlat...
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