Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia

Uveal melanoma (UM) is unique among cancers in displaying reduced endogenous levels of sister chromatid exchange (SCE). Here we demonstrate that FANCD2 expression is reduced in UM and that ectopic expression of FANCD2 increased SCE. Similarly, FANCD2-deficient fibroblasts (PD20) derived from Fanconi anaemia patients displayed reduced spontaneous SCE formation relative to their FANCD2-complemented counterparts, suggesting that this observation is not specific to UM. In addition, spontaneous RAD51 foci were reduced in UM and PD20 cells compared with FANCD2-proficient cells. This is consistent with a model where spontaneous SCEs are the end product of endogenous recombination events and implicates FANCD2 in the promotion of recombination-mediated repair of endogenous DNA damage and in SCE formation during normal DNA replication. In both UM and PD20 cells, low SCE was reversed by inhibiting DNA-PKcs (DNA-dependent protein kinase, catalytic subunit). Finally, we demonstrate that both PD20 and UM are sensitive to acetaldehyde, supporting a role for FANCD2 in repair of lesions induced by such endogenous metabolites. Together, these data suggest FANCD2 may promote spontaneous SCE by influencing which double-strand break repair pathway predominates during normal S-phase progression

Assessment of DNA damage using chromosomal aberrations assay in lymphocytes of waterpipe smokers

OBJECTIVES: The aim of this study was to investigate the genotoxicity of waterpipe smoking in the lymphocytes of waterpipe smokers using chromosomal aberrations (CAs) assay. MATERIALS AND METHODS: Fifty waterpipe smokers and 18 healthy non-smokers volunteered to participate in the study. Additionally, 18 heavy cigarette smokers were recruited for comparison. Chromosomal aberrations (CAs) assay was used to evaluate DNA damage in the lymphocytes. RESULTS: The results showed that similarly to cigarette smoking, waterpipe smoking significantly increased the frequencies of CAs (p < 0.01). In addition, the frequencies of CAs increased with more waterpipe use. CONCLUSIONS: Waterpipe smoking causes DNA damage to lymphocytes and the damage increases with more waterpipe use