Folate deficiency in human peripheral blood lymphocytes induces chromosome 8 aneuploidy but this effect is not modified by riboflavin.
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.
Ni
Juan
J
School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, People's Republic of China.
Lu
Lin
L
Fenech
Michael
M
Wang
Xu
X
D000328:Adult; D000782:Aneuploidy; D002478:Cells, Cultured; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000150:complications*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008875:Middle Aged; D012256:Riboflavin / Q000494:pharmacology; D012257:Riboflavin Deficiency / Q000150:complications; D014803:Vitamin B Complex / Q000494:pharmacology
D014803:Vitamin B Complex; D005492:Folic Acid; D012256:Riboflavin