Fanconi anemia lymphocytes: effect of DL-alpha-tocopherol (Vitamin E) on chromatid breaks and on G(2) repair efficiency

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 muM DL-alpha -tocopherol (Vitamin E) on the level of chro mosomal damage in mitosis was studied in lymphocytes from five FA patients and from age matched controls, both under basal conditions and when G(2) re pair was prevented by 2.5 mM caffeine (G(2) unrepaired damage). In addition , the effect of this antioxidant on G(2) duration and the efficiency of G(2 ) repair was also evaluated in the sample. alpha -Tocopherol (AT) decreased the frequency of chromosomal damage (under basal and inhibited G(2) repair conditions) and the duration of G(2) in FA cells. This antioxidant protective effect, expressed as the decrease in ch romatid breaks, was greater in FA cells (50.8%) than in controls (25%). The efficiency of the G(2) repair process (G(2)R rate) defined as the ratio between the percentage of chromatid breaks repaired in G(2) and the durati on of this cell cycle phase was lesser in FA cells (10.6) than in controls (22.6). AT treatment slightly increased this G(2)R rate, both in FA cells a nd controls. These results suggest that an increased oxidative damage and a lower G(2) r epair rate may be simultaneously involved in the high frequency of chromati d damage detected in FA cells. (C) 2001 Elsevier Science B.V. All rights re served.