How a huge number. F,G: The positive MCM7 nuclei (arrowheads) are evident in dysplastic (F) and nondysplastic acini (G). H,I: Ubiquitin expression, in H control acini has immunopositive expression in the cytoplasm (black arrowhead) and in the nucleus (white arrowheads). The nucleus interior is not uniform. Dysplastic lesions (I) present positive nucleus for ubiquitin (arrowheads). J,K: The localization of Bcl-2 immunoreactivity is similar in normal and dysplastic epithelium. Normal acini of Cd-treated rats 1676428 are homogeneous in the cytoplasm (arrowheads in J). Dysplastic acinus shows mainly granular immunoreactivity in the apical border of the epithelium. L,M: DNA fragmentation test. Control acinus with abundant positive nuclei (arrowheads). Dysplastic acini show few apoptotic nuclei (arrowheads). N,O: p53 immunoreactive nuclei (black arrowheads) and cytoplasm (white arrowheads) cells are detected in the dysplastic lesions (L) and in normal epithelium (O). P,Q: 15481974 Endothelial positive cells to FVIII are recognized in dysplastic stromal tissue (P) and normal acini (Q). Sections counter stained: Harris hematoxylin (A,B,C,P,Q), methyl green (D,E,H,I), and 
acetic carmine (F,G,J,K,L,M,N,O). doi:10.1371/journal.pone.0057742.gNuclear immunoreactivity to PCNA (Figs. 1D, 1E) and MCM7 (Figs. 1F, 1G) was detected in epithelial cells from the prostate acini throughout all the groups studied. PCNA immunostaining was also remarkable in the acini with dysplastic changes (Fig. 1D), as well as MCM7 (Fig. 1F). Ubiquitin expression was observable in the cytoplasm and in the nucleus of the epithelial cells, mainly in the peripheral acini (Figs. 1H, 1I). Dysplastic acini showed nucleus immunostaining for ubiquitin, but no cytoplasm staining was detected (Fig. 1I). Immunoreactivity to Bcl-2 protein was observed in control and Cd-treated rats. It was granular and expressed in the apical border of the epithelium in the control group and nondysplastic acini. In dysplastic glands, Bcl-2 immunostaining was more widely extended throughout all the 
cytoplasm, although it was more prominent near the lumen of the cribriform structures (Fig. 1J, 1K). Apoptotic nuclei were observed in epithelial cells from the control group and treated animals (Figs. 1L). Scarce apoptotic nuclei were also visualized in dysplastic lesions (Fig. 1M).Immunoreactivity to p53 was detected in cytoplasm and nuclear epithelial cells from the prostate acini throughout all the groups studied. Nuclear p53 immunostaining was also remarkable in the acini with dysplastic changes (Fig. 1N, 1O). Microvessels immunostained to Factor VIII were observed in both control and Cd-treated rat. More capillaries were apparently seen in both dysplastic acini (Fig. 1P, 1Q).Quantitative resultsA significant increase for LILPA1 (p,0.01) in the normal acini and dysplastic acini of Cd-treated rats was detected in Epigenetics comparison to the control acini (Fig. 2). The LIPCNA was significantly increased in dysplastic lesions (p,0.05), whereas the control acini and cadmium nondysplastic acini did not show significant variations (Fig. 3A). LIMCM7 was significantly increased in the animals exposed to cadmium (normal acini and dysplastic acini) in comparison to control animals (Fig. 3B). There was no significant difference in the VF Bcl-2 between the control and cadmium-treated animals (Fig. 4A). A significantLPA1 in Prostate Dysplastic inhibitor LesionsFigure 2. Bar diagram indicating the mean ?SD of the LILPA1 in normal acini of control rats (Ctr.How a huge number. F,G: The positive MCM7 nuclei (arrowheads) are evident in dysplastic (F) and nondysplastic acini (G). H,I: Ubiquitin expression, in H control acini has immunopositive expression in the cytoplasm (black arrowhead) and in the nucleus (white arrowheads). The nucleus interior is not uniform. Dysplastic lesions (I) present positive nucleus for ubiquitin (arrowheads). J,K: The localization of Bcl-2 immunoreactivity is similar in normal and dysplastic epithelium. Normal acini of Cd-treated rats 1676428 are homogeneous in the cytoplasm (arrowheads in J). Dysplastic acinus shows mainly granular immunoreactivity in the apical border of the epithelium. L,M: DNA fragmentation test. Control acinus with abundant positive nuclei (arrowheads). Dysplastic acini show few apoptotic nuclei (arrowheads). N,O: p53 immunoreactive nuclei (black arrowheads) and cytoplasm (white arrowheads) cells are detected in the dysplastic lesions (L) and in normal epithelium (O). P,Q: 15481974 Endothelial positive cells to FVIII are recognized in dysplastic stromal tissue (P) and normal acini (Q). Sections counter stained: Harris hematoxylin (A,B,C,P,Q), methyl green (D,E,H,I), and acetic carmine (F,G,J,K,L,M,N,O). doi:10.1371/journal.pone.0057742.gNuclear immunoreactivity to PCNA (Figs. 1D, 1E) and MCM7 (Figs. 1F, 1G) was detected in epithelial cells from the prostate acini throughout all the groups studied. PCNA immunostaining was also remarkable in the acini with dysplastic changes (Fig. 1D), as well as MCM7 (Fig. 1F). Ubiquitin expression was observable in the cytoplasm and in the nucleus of the epithelial cells, mainly in the peripheral acini (Figs. 1H, 1I). Dysplastic acini showed nucleus immunostaining for ubiquitin, but no cytoplasm staining was detected (Fig. 1I). Immunoreactivity to Bcl-2 protein was observed in control and Cd-treated rats. It was granular and expressed in the apical border of the epithelium in the control group and nondysplastic acini. In dysplastic glands, Bcl-2 immunostaining was more widely extended throughout all the cytoplasm, although it was more prominent near the lumen of the cribriform structures (Fig. 1J, 1K). Apoptotic nuclei were observed in epithelial cells from the control group and treated animals (Figs. 1L). Scarce apoptotic nuclei were also visualized in dysplastic lesions (Fig. 1M).Immunoreactivity to p53 was detected in cytoplasm and nuclear epithelial cells from the prostate acini throughout all the groups studied. Nuclear p53 immunostaining was also remarkable in the acini with dysplastic changes (Fig. 1N, 1O). Microvessels immunostained to Factor VIII were observed in both control and Cd-treated rat. More capillaries were apparently seen in both dysplastic acini (Fig. 1P, 1Q).Quantitative resultsA significant increase for LILPA1 (p,0.01) in the normal acini and dysplastic acini of Cd-treated rats was detected in comparison to the control acini (Fig. 2). The LIPCNA was significantly increased in dysplastic lesions (p,0.05), whereas the control acini and cadmium nondysplastic acini did not show significant variations (Fig. 3A). LIMCM7 was significantly increased in the animals exposed to cadmium (normal acini and dysplastic acini) in comparison to control animals (Fig. 3B). There was no significant difference in the VF Bcl-2 between the control and cadmium-treated animals (Fig. 4A). A significantLPA1 in Prostate Dysplastic LesionsFigure 2. Bar diagram indicating the mean ?SD of the LILPA1 in normal acini of control rats (Ctr.
