Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: II. Contribution of sex, age, and lifestyle.

Sister chromatid exchange (SCE) and micronuclei (MN) analysis was carried out on 1,650 healthy individuals living in Pisa and in two nearby small cities, Cascina and Navacchio (Ca-Na). The effect of smoking on SCEs was linearly correlated with the number of cigarettes per day, and an increase of 7.3% SCEs was detectable for as few cigarettes as 1-10/day. Ex-smokers showed intermediate mean values of SCEs (8.09 +/- 1.88) in comparison with never smokers (7.54 +/- 1.61) and current smokers (8.45 +/- 1.94). Mean values of SCEs of ex-smokers decreased linearly with time of smoking cessation, reaching the mean values of never smokers within 8 years. The extent of SCE decrease was inversely proportional to the number of cigarettes previously smoked. No interaction between smoking habits and coffee or alcohol drinking on SCEs was observed. A borderline (P = 0.053) increase in mean SCE values in coffee drinkers (more than 3 cups/day) was found. The age effect on SCEs was remarkable in Ca-Na, but not in Pisa donors. Job type was not associated with significant modification of mean values of SCEs. Multiple logistic regression analysis revealed a statistically significant association between the proportion of high frequency cells (HCF) outliers and coffee consumption. Age and sex appeared to be by far the most important variables associated with modifications in MN frequency, which increased by 0.04 per thousand and 0.02 per thousand per year in males and females, respectively. Children and young donors (age < or = 40 years) showed lower MN frequency regardless of sex, whereas sex appeared to determine a significantly higher increase of MN only in females older than 40 years. In contrast, in males the MN rate by age tended to level off after the age of 30-50. MN frequencies of Pisa blue- and white-collar workers were statistically significantly higher than in students (+0.71 and +0.55 per thousand, respectively). Smoking did not determine any increase of MN frequency. A total lack of correlation (P = 0.913) between MN and SCEs was observed.

In vivo genotoxic interactions among three phenolic benzene metabolites.

Three benzene metabolites, hydroquinone (HQ), cathecol (CAT) and phenol (PHE) were studied to define their possible interaction in inducing micronuclei (Mn) in mouse bone marrow polychromatic erythrocytes (PCEs). HQ and CAT, administered separately, induced Mn while PHE showed no genotoxic effects. Binary and ternary mixtures of two or three metabolites gave different results, causing considerable increase or decrease in Mn induction. HQ and PHE, in binary mixtures, as well as PHE and CAT, increased Mn synergistically, while HQ and CAT interacted negatively. The genotoxicity of ternary mixtures was mainly the consequence of two metabolites: HQ and CAT. The maximal effect obtained is far below the induction of Mn consequent to benzene treatment. These data suggest that toxic and genotoxic effects of benzene alone could be the result of more complex interactions among these and other metabolites.