Modulating factors of individual sensitivity to diepoxybutane: chromosome aberrations induced in vitro in human lymphocytes.

Peripheral blood lymphocytes from a sample of 62 randomly selected donors were analysed for spontaneous and diepoxybutane (DEB)-induced chromosomal aberrations (CA). These individuals were part of a larger sample of 122 subjects whose DEB responsiveness was evaluated by means of sister chromatid exchange (SCE) analysis. Confounding factors (such as smoking, wine and coffee consumption, occupation and haematological factors) were analysed for their effect on individual DEB-responsiveness, but no statistically significant associations were observed. Interestingly, a bimodal distribution of aberrant cell frequencies was clearly detectable, showing the existence of DEB-sensitive subjects belonging to the second mode (CA frequencies > 19%). When responsiveness evaluated by means of CA induction was compared with SCE responsiveness, it was noted that all SCE-inducible subjects (> 110.9 SCEs/cell) belonged to the second mode of CA frequency distribution. On the other hand, highly CA inducible individuals did not necessarily show a higher SCE-response, although their DEB-induced SCE frequencies were above average (92 SCEs/cell). DEB-induced CA frequency correlated with baseline levels, indicating that DEB-sensitive individuals also showed higher spontaneous chromosome damage (3.6 versus DEB-resistant 2%, P < 0.05). Finally, when simple and multiple regression analyses were carried out, DEB-sensitivity appeared negatively related to haematic concentrations of proteins and uric acid (intercept 0.131 +/- 0.011, slope -0.029 +/- 0.0116, r = -0.39; P < 0.01), probably due to its antioxidant activity. This finding confirmed previous observations on the scavenger activity of plasma factors on DEB mutagenicity.

Chromosome aberrations in humans in relation to site of residence.

Baseline frequencies of chromosome aberrations (CAs) were assessed in three samples of healthy individuals, 60 living in a rural area (Po Delta), 134 in Pisa downtown and 116 in Cascina, a small town near Pisa, Italy. The three groups were similar for average age, sex ratio, smoking, drinking habit, and occupation. Multifactor ANOVA showed that CA frequencies increased significantly with age (p < 0.0001 excluding and including gaps), and with smoking habit (p = 0.0045 including gaps; p = 0.04 excluding gaps). Gender, drinking habit and occupation exerted no statistically significant effects. Multifactor ANOVA showed also a significant effect of the site of residence on the frequency of the CA, including gaps (p = 0.0003) and excluding gaps (p = 0.03). The CA frequency of the Pisa samples was statistically significantly higher than that of the Po Delta samples. Air pollution was considered to be a possible factor in determining the observed differences among the sites of residence, as levels of air pollutants (SO2 and TSP, total suspended articles) were more elevated in Pisa and Cascina than in the Po Delta. In addition, respiratory symptoms used as indirect indicators of air pollution at individual level were significantly more frequent in the Pisa population than in Cascina or in the Po Delta. These findings might support the hypothesis that air-pollution levels, even within E.E.C. (European Economic Community) air-quality standards, may influence baseline CA frequencies.