Mutagenesis Advance Access originally published online on December 8, 2005
Mutagenesis 2006 21(1):41-47; doi:10.1093/mutage/gei069
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan
1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China, 2School of Life Sciences, Yunnan Normal University, Kunming, Yunnan 650092, People's Republic of China, 3CSIRO Human Nutrition, PO BOX 10041, Adelaide BC, SA 5000, Australia and 4The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, People's Republic of China
We hypothesized that the genomic response to folate deficiency might be different between breast cancer cases and healthy subjects. To test this hypothesis, we performed a comprehensive study on the genotoxic and cytotoxic effects of in vitro folic acid (FA) deficiency on primary human lymphocytes from 19 breast cancer patients and 20 age-matched healthy females from Yunnan, China using the cytokinesis-block micronucleus assay. Lymphocytes from the volunteers were cultured in RPMI1640 medium containing 30, 120 or 240 nM FA for 9 days. The results showed that 30 nM FA was associated with increased frequencies of micronucleated binucleated cell (MNed BNC), nucleoplasmic bridges (NPB), nuclear buds (BUD), apoptosis (APO) and necrosis (NEC) relative to 120 and 240 nM FA (P < 0.001) in lymphocytes of case and control groups in vitro, however there were no significant differences between the 120 and 240 nM FA within each sampling group. The case group showed significantly higher frequencies of MNed BNC than control at 120 and 240 nM FA (P < 0.05–0.001) but not at 30 nM FA (P = 0.052). NEC was significantly higher in breast cancer group than control at all concentrations of FA (P < 0.005). FA concentration explained 60, 39, 39, 52 and 71% of the variance of MNed BNC, NPB, BUD, APO and NEC, respectively compared with breast cancer status which only explained 6 and 7% of the variance of MNed BNC and NEC(Two way ANOVA, P < 0.0001). Difference of difference analysis showed that breast cancer cases were not abnormally sensitive to the genome-damaging effect of folate deficiency. We concluded that (i) increased concentrations of FA abolished the genome-damaging effect of FA deficiency in lymphocytes of both breast cancer patients and controls to a similar extent and (ii) FA concentration is much more important than breast cancer status in determining genomic instability and cell death.
* To whom correspondence should be addressed. Michael Fenech, Tel: +618 8303 8880; Fax: +618 8303 8899; Email: michael.fenech{at}csiro.au Correspondence may also be addressed to Jinglun Xue, Tel/Fax: +8621 6564 9899; Email: jlxue{at}fudan.ac.cn