Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a @entity5345 mutation in XXXX families.

@entity1 @entity0 @entity5344 @entity5 @entity5345 @entity273 @entity56
Enhanced sensitivity to the chromosome-damaging effects of ionizing radiation is a feature of many @entity5 -predisposing conditions. It has been suggested that @entity1 with @entity0 are deficient in the repair of radiation-induced DNA damage. We have now investigated whether mutagen sensitivity is related to mutations in the @entity0 gene @entity5345 . We studied the induction and repair of DNA damage in lymphocytes of @entity1 from families with @entity0 and @entity5344 . The mutagens used were gamma-irradiation and @entity273 and the DNA effects were determined with the micronucleus test and the comet assay. @entity1 with a @entity5345 mutation (n = 12) and relatives without the familial mutation (n = 10) were compared to controls (i.e., healthy @entity1 without family history of @entity5344 ; n = 17). Our results indicate a close relationship between the presence of a @entity5345 mutation and sensitivity for the induction of micronuclei. Compared to a concurrent control, 10 of 11 @entity1 with a @entity5345 mutation showed elevated radiation sensitivity. Of the 10 related @entity1 without the familial mutation, only 2 had clearly enhanced micronucleus frequencies. In addition to the sensitivity toward gamma-irradiation, @entity56 toward @entity273 was also observed, indicating that the mutagen sensitivity is not solely due to a defect in the repair of DNA double strand breaks. In contrast to the results with the micronucleus assay, we found no significant difference between @entity1 with and without a @entity5345 mutation with respect to the induction and repair of DNA damage in the comet assay. This finding suggests a normal rate of damage removal and points to a disturbed fidelity of DNA repair as a direct or indirect consequence of a @entity5345 mutation. Our results support the usefulness of induced micronucleus frequencies as a biomarker for @entity5 predisposition and suggest its application as a screening test for carriers of a @entity5345 mutation in @entity0 families.
