## 4 Discussion
At the cumulative doses of IR exposure, no influence of the polymorphisms studied was found on the frequency of spontaneous CAs and MN and on the Comet assay parameters, with the exception of an increase in the frequency of MN in the exposed workers bearing one or simultaneously more allelic variants of the three _XRCCI_ polymorphisms. Previous studies of _XRCCI_ polymorphisms in workers exposed to IR did not generally reveal any influence of _XRCCI_ 399 and _XRCCI_ 194, analyzed singly, on the frequency of spontaneous MN [12; 43; 42]. Therefore, the genetic susceptibility to low doses to IRcould be influenced by the interaction of effects of different enzymatic genetic polymorphisms. The lack of genetic susceptibility observed in our study could also depend on the small number of individuals carrying each allelic variant, that did not allow combined analysis of interactions among the different genes involved, except for the activity of _XRCC1_, nor a separate analysis of the presence of polymorphic alleles in homozyggosis or heterozygositygosis that could have a different effect on the enzymatic phenotype. In the exposed workers, individual mutagen sensitivity was not shown in our study, in agreement with other authors, a reduction in BLM-induced clastogenic damage, unlike what was observed by [PERSON] et al. [16] for exposure to higher doses of IR (mean exposure 4.46 mSv/year, range 0-28 mSv/year) [17; 44]. Nevertheless, in our work a negative dependency was found of the frequency of BLM-induced MN on chronic exposure to low doses of IR, associated with a positive dependency determined by the presence of the _GSTM1_ null genotype and of a lifestyle factor such as alcohol consumption. In fact, both these factors determine an increased frequency of BLM-induced MN and seem to be able to make an opposite effect in respect to that induced by IR. The influence of the A1450G polymorphism of BLHX on individual mutagen sensitivity in subjects exposed to IR was also analyzed. Unexpectedly, the results did not show any influence of this polymorphism, unlike the findings by [PERSON] et al. [6], who had observed an increased frequency of BLM-induced MN in 45 healthy subjects, nonsmokers, with no genotoxic exposure, who were carriers of the allelic variant of the above BLHX polymorphism in homozyggosis or heterozygositygosis. Cigarette smoking was not found to affect the frequency of spontaneous CAs and MN. This could be due to the small number of heavy smokers among our exposed workers and controls, since it has been demonstrated in the literature that an increased frequency of MN is present only in smokers of more than 30 cigarettes/day [45]. Nor was any relation between smoking habit and the Comet assay parameters found, in partial agreement with the literature, although discordant results have also been reported [40]. Indeed, our results did not show an interaction between exposure to IR and a smoking habit in determining either spontaneous or BLM-induced genotoxic damage, unlike what was observed by other authors in workers exposed to higher doses of IR [16; 44; 35]. Instead, the cytogenetic biomarkers of BLM-induced chromatid breakage were all found to be negatively correlated with the number of cigarettes/day, whereas no correlation was found with the number of packets/year. This finding; however, seems to indicate that the daily smoking habit may have the effect to increase the DNA repair efficiency, independently from exposure to IR. When analyzing the exposed workers and controls as a single group, a positive correlation was found between the frequency of spontaneous MN and age, in agreement with reports in literature [45]. Age is naturally a factor that can influence the frequency of MN in peripheral lymphocytes as a consequence both of the cumulative effects of acquired gene mutations involving DNA repair and cell replication mechanisms, and of the progressive accumulation of chromosome damage caused by exposure to endogenous and environmental genotoxic substances [46].