Genetic instability, whether constitutional or induced, has long been suspected to predispose to carcinogenesis. Cytogenetic assays are classical methods to detect chromosome aberrations that have been used as end points of exposure to genotoxic agents. In the current study, we tested the sensitivity of the micronucleus assay (MN) in detecting baseline and γ-ray induced damage in the peripheral blood lymphocytes from 76 brain tumor patients and 76 age-, sex- and ethnicity matched controls. In addition, we investigated the effect of genetic polymorphisms in DNA repair genes (XRCC1, XRCC3, XRCC7) and cell cycle control genes (P53 and RAD51) on modulating the level of baseline and γ-ray induced genetic damage. MN originate from chromosome fragments or whole chromosomes during nuclear division, therefore the assay provides a measure of both structural chromosome breakage and numerical chromosome losses or gains, and is a good indicator of chromosome damage and cell cycle defects (reflected as binucleated bridges). Our results showed that the frequency of baseline micronuclei was significantly elevated in cases (mean ± SD = 3.22 ± 1.7) as compared to controls (mean ± SD = 2.67± 2.0; p= 0.05). Similarly the frequency of baseline binucleated bridges was significantly higher in cases (mean ± SD = 2.18 ± 1.7) as compared to controls (mean ± SD = 0.86± 1.0; p<0.0001). The mean ± SD level of micronuclei frequency was significantly higher in γ-ray treated cultures from cases 10.16 ± 3.5 as compared to 7.53± 3.75 in controls; p<0.0001. Similarly, the mean ± SD frequency of binucleated bridges was significantly higher in γ-ray treated cultures from cases 11.93 ± 4.78 as compared to 7.79 ± 3.29 in controls; p<0.0001. Of the 5 different polymorphic genes tested, only p53 and RAD51 allelic variants had a modulating effect on γ-ray induced MN and binucleated bridge frequencies. These results indicate that MN assay is a sensitive measure for detection of genetic damage and that genetic polymorphisms play an important role in modulating such damage.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]