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Among endocrine disruptors, the xenoestrogen bisphenol A (BPA) is of particular interest due to the very high production and widespread environmental contamination. We recently demonstrated that the oral administration of BPA to mice results in the formation of DNA adducts not only in liver but also in mammary tissue. The present study aimed at evaluating the modulation of BPA-related DNA adducts and proteome alterations by the chemopreventive agents budesonide (BUD) and phenethyl isothiocyanate (PEITC). Swiss ICR (CD-1) mice received, for 8 days, BPA with the drinking water and either chemopreventive agent with the diet. We measured DNA adducts by (32)P postlabeling and 656 proteins by antibody microarray. BPA induced the formation, with similar patterns, of DNA adducts in liver and in mammary tissue. Moreover, BPA dysregulated 13 proteins in mammary tissue, mostly in the sense of upregulation, including estrogen receptor-beta and proteins involved in cell proliferation, inhibition of apoptosis, tissue remodeling, inflammation, stress response, and glutathione synthesis. PEITC significantly inhibited the formation of BPA-induced DNA adducts, but only at the highest dose tested, and BUD was totally ineffective. The chemopreventive agents modulated a variety of BPA-induced changes in proteome profiles. However, as shown by both hierarchical cluster analysis and principal component analysis, BUD and especially PEITC were not able to restore the physiological situation in BPA-treated mice. Therefore, the in vivo use of proteome analysis proves to be a sensitive tool for the early prediction not only of protective effects but also of adverse effects of chemopreventive agents.

Chlorination by-products (CBPs) in drinking water have been associated with an increased risk of adverse pregnancy outcomes, including small for gestational age at term (term-SGA) and preterm delivery. Epidemiological evidence is weakened by a generally inaccurate exposure assessment, often at an ecological level. A case control study with incident cases was performed in nine Italian towns between October 1999 and September 2000. A total of 1,194 subjects were enrolled: 343 preterm births (26th-37th not completed week of pregnancy), 239 term-SGA (from 37th completed week, and weight less than the lowest 10th percentile) and 612 controls. Exposure was assessed both by applying a questionnaire on mothers' personal habits during pregnancy and by water sampling directly at mothers' homes. Levels of trihalomethanes (THMs) were low (median: 1.10 microg l(-1)), while chlorite and chlorate concentrations were relatively high (median: 216.5 microg l(-1) for chlorites and 76.5 microg l(-1) for chlorates). Preterm birth showed no association with CBPs, while term-SGA, when chlorite levels > or =200 microg l(-1) combined with low and high levels of inhalation exposure are considered, suggested a dose-response relationship (adjusted-Odds Ratios (ORs): 1.52, 95%CI: 0.91-2.54 and 1.70, 95%CI: 0.97-3.0, respectively). A weak association with high exposure levels of either THMs (> or =30 microg l(-1)), or chlorite or chlorate (> or =200 microg l(-1)) was also found (adjusted-OR: 1.38, 95%CI: 0.92-2.07). Chlorine dioxide treatment is widespread in Italy; therefore, chlorite levels should be regularly and carefully monitored and their potential effects on pregnancy further evaluated and better understood.