Folate deficiency in human peripheral blood lymphocytes induces chromosome 8 aneuploidy but this effect is not modified by riboflavin

Abstract

Chromosome 8 aneuploidy is a common event in certain cancers but whether folate (F) deficiency induces chromosome 8 aneuploidy is not known. Furthermore the impact of riboflavin (R) deficiency, which may alter activity of a key enzyme in folate metabolism, on these events is unknown. Therefore, the aim of our research was to test the following hypotheses: (a) F deficiency induces chromosome 8 aneuploidy; (b) chromosome 8 aneuploidy is affected by F deficiency to a similar degree as chromosome 17 and (c) R deficiency aggravates the risk of aneuploidy caused by F deficiency. These hypotheses were tested in long-term cultures of lymphocytes from twenty female healthy volunteers (aged 30-48 years). Lymphocytes were cultured in each of the four possible combinations of low (L) and high (H) F (LF, 20 nmol/L, HF 200 nmol/L, respectively) and L and H R (LR 1 nmol/L, HR 500 nmol/L, respectively) media (LFLR, LFHR, HFLR, HFHR) for 9 days. Chromosomes 8 and 17 aneuploidy was measured in mononucleated (MONO) and cytokinesis-blocked binucleated (BN) cells using dual-color fluorescence in situ hybridization (FISH) with fluorescent centromeric probes specific for chromosomes 8 and 17. Culture in LF media (LFLR or LFHR) induced significant and similar increases in frequencies of aneuploidy of chromosomes 8 and 17 (P < 0.001) relative to culture in HF media (HFLR or HFHR). There was no significant effect of R concentration on aneuploidy frequency for either chromosome. We conclude that F deficiency is a possible cause of chromosome 8 aneuploidy.

Interactions Between MTHFR C677T - A1298C Variants and Folic Acid Deficiency Affect Breast Cancer Risk in a Chinese Population

“…Xia-Yu Wu 1,2 , Juan Ni 2 , Wei-Jiang Xu 2 , Tao Zhou 2 , Xu Wang 1,2 * also be associated with aneuploidies of the increment chromosomes 17, 21 and 8 (Wang et al, 2004;Ruosaari et al, 2008;Ni et al, 2010). Low dietary FA intake also results in an interruption of the DNA repair capability (Wei et al, 2003).…”

Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

“…[11] Folate functions to provide one-carbon groups for DNA synthesis/methylation and the epigenetic control of gene expression [11–13]. Since the liver is the major site of folate storage and is, therefore, susceptible to folate deficiency, deprivation of this micronutrient may contribute to chromosomal breaks, aneuploidy and deleterious alterations in gene expression within hepatocytes; this, in turn, leads to genetic instability and carcinogenesis [14–17]. For instance, the impact of folate deficiency on biomarkers of telomeres provides evidence of dysfunctional long and short telomeres as a cause of telomere critical length/chromosome instability.…”

Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature

“…This was also observed for chromosome 8 [44], found abnormal in number in prostate, skin and breast cancers, cholesteatoma and leukaemia [45–48]. In particular, trisomy 8 has been reported as a recurrent chromosomal abnormality in acute myeloid leukaemia (AML) and hence considered a cytogenetic marker of AML [49, 50].…”

“…In particular, trisomy 8 has been reported as a recurrent chromosomal abnormality in acute myeloid leukaemia (AML) and hence considered a cytogenetic marker of AML [49, 50]. Ni et al [44] demonstrated that aneuploidy of chromosome 8 is influenced by folic acid deficiency similarly to chromosome 17. In addition, riboflavin deficiency seemed not to aggravate the risk of aneuploidy, which is coherent with other studies in which riboflavin had no influence on the formation of micronuclei [51].…”