Fanconi anemia lymphocytes: effect of dl-α-tocopherol (Vitamin E) on chromatid breaks and on G2 repair efficiency

Abstract

The high frequency of chromosomal breaks in Fanconi anemia (FA) lymphocytes has been related to the increased oxidative damage shown by these cells.

The effect of 100 μM dl-α-tocopherol (Vitamin E) on the level of chromosomal damage in mitosis was studied in lymphocytes from five FA patients and from age matched controls, both under basal conditions and when G₂ repair was prevented by 2.5 mM caffeine (G₂ unrepaired damage). In addition, the effect of this antioxidant on G₂ duration and the efficiency of G₂ repair was also evaluated in the sample.

α-Tocopherol (AT) decreased the frequency of chromosomal damage (under basal and inhibited G₂ repair conditions) and the duration of G₂ in FA cells. This antioxidant protective effect, expressed as the decrease in chromatid breaks, was greater in FA cells (50.8%) than in controls (25%).

The efficiency of the G₂ repair process (G₂R rate) defined as the ratio between the percentage of chromatid breaks repaired in G₂ and the duration of this cell cycle phase was lesser in FA cells (10.6) than in controls (22.6). AT treatment slightly increased this G₂R rate, both in FA cells and controls.

These results suggest that an increased oxidative damage and a lower G₂ repair rate may be simultaneously involved in the high frequency of chromatid damage detected in FA cells.