The higher lead levels in blood and calcified tissues observed in the F + Pb group compared with the other groups13 indicate higher availability of lead and higher incorporation of this metal into tissues when it is associated with F. Hypomineralization was shown starting from the very surface of enamel (i.e., Veliparib in vivo no subsurface lesions), reflecting the condition of rat enamel during the final wave of mineralization at the maturation stage.20 The cavities have also

been described in the case of hypomineralized mouse enamel formed in the absence of the gene for kallikrein 4.21 The presence of cavities can be explained by the interaction between mechanical loading and the hypomineralized enamel. An improvement in motor activity in rats exposed to Pb22 and the reduced enamel hardness resultant from hypomineralization23 are consistent with a higher probability of brittle fracture and cavity formation in enamel. In this context, Y-27632 in vitro it is important to note that cavities were demonstrated to be surrounded by hypomineralized enamel (Fig. 2e–f). In the literature, rodent enamel

fluorosis has been scored by means of a macroscopically applied shade guide, so as to measure increasing whiteness of the incisor buccal surface.24 In relation to ours, such scoring system, which was validated by quantitative light-induced fluorescence on the non-sectioned buccal surface, poses three major limitations: (i) it cannot be used to localize a single fluorotic lesion; (ii) the surface features are not related to inner histological ones, and (iii) the number of cavities is not taken into account. Spatially-resolved correlations between surface and internal enamel Phosphoprotein phosphatase defects might be helpful for a deeper understanding of the mechanism of enamel fluorosis. Rises in fluoride concentrations do not seem to be responsible for the appearance of the more severe defects in the F + Pb group, since no increased amounts of fluoride

could be detected in the calcified tissues of the animals co-exposed to lead. Furthermore, fluorosis severity has been shown to be influenced by a variety of factors, such as the genetic background in rats.24 The more severe defects observed in the F + Pb group would more likely be caused by an additive or synergistic effect of the co-exposure to fluoride and lead. Lead alone did not produce any alterations. Although it is known that lead concentration in calcified tissues is 2–3.4 times higher in the F + Pb group compared with the Pb group,13 these concentrations still would not elicit enamel defects in the absence of fluoride. Lead given to rats at 34 and 170 ppm in the drinking water for 70 days did not modify the superficial physical properties of mature enamel,10 even though enamel mineralization was delayed, and more protein was found in the secretory early maturation stage compared with controls.