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

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.