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Titolo:
The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro
Autore:
Crott, JW; Mashiyama, ST; Ames, BN; Fenech, M;
Indirizzi:
CSIRO Hlth Sci & Nutr, Commonwealth Sci Ind Res Org, Adelaide, SA 5000, Australia CSIRO Hlth Sci & Nutr Adelaide SA Australia 5000 aide, SA 5000, Australia Univ Adelaide, Dept Physiol, Adelaide, SA 5005, Australia Univ Adelaide Adelaide SA Australia 5005 ol, Adelaide, SA 5005, Australia Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA Childrens Hosp Oakland Oakland CA USA 94609 s Inst, Oakland, CA 94609 USA
Titolo Testata:
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
fascicolo: 10, volume: 10, anno: 2001,
pagine: 1089 - 1096
SICI:
1055-9965(200110)10:10<1089:TEOFAD>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAMMALIAN GENE AMPLIFICATION; METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; CHINESE-HAMSTER CELLS; PREDICT HUMAN CANCER; URACIL MISINCORPORATION; PLASMA HOMOCYSTEINE; COLORECTAL-CANCER; COMMON MUTATION; RISK FACTOR; DNA-DAMAGE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Fenech, M CSIRO Hlth Sci & Nutr, Commonwealth Sci Ind Res Org, POB 10041, Adelaide, SA 5000, Australia CSIRO Hlth Sci & Nutr POB 10041 Adelaide SA Australia 5000 ralia
Citazione:
J.W. Crott et al., "The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro", CANC EPID B, 10(10), 2001, pp. 1089-1096

Abstract

We performed a comprehensive study on the genotoxic and cytotoxic effects of in vitro folic acid deficiency on primary human lymphocytes. Lymphocyteswere cultured in medium containing 12-120 nM folic acid for 9 days in a novel cytokinesis-block micronucleus (CBMN) assay system (n = 20). Besides identifying optimal folic acid concentrations for in vitro genomic stability,we tested the hypothesis that lymphocytes from individuals homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (TTs, n = 10) are protected against chromosome damage relative to controls (CCs, n = 10) under conditions of folic acid deficiency. This hypothesis is based on the assumption that reduced :MTHFR activity in TT lymphocytes causes a diversion of 5,10-methylene tetrahydrofolate toward thymidine synthesis, which minimizes uracil-induced double-stranded DNA breakage. Cells were scored for micronuclei, apoptosis, necrosis, nucleoplasmic bridges, and nuclear budding. The latter two endpoints are indicative of chromosome rearrangementsand gene amplification, respectively, and to the best of our knowledge, this is the first report of their association with folic acid concentration. Folic acid concentration correlated significantly (P < 0.0001) and negatively (r, -0.63 to -0.74) with all markers of chromosome damage, which were minimized at 60-120 nM folic acid, much greater than concentrations assumed "normal," but not necessarily optimal in plasma. Two-way ANOVA revealed no effect of the MTHFR genotype on any of the endpoints. Results show that the C677T polymorphism does not affect the ability of a cell to resist chromosome damage induced by folic acid deficiency in this in vitro system.

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Documento generato il 15/07/20 alle ore 21:26:18