Figure 1.

Oxidative stress and DDR in silica-induced lesions measured by immunohistochemistry in serial consecutive sections. The figures in this plate show the activation of the iNOS/p53/γ-H2AX pathway in the multistep progression from normal tissue to tumors. Low levels of iNOS and p53 proteins were found in morphologically normal bronchial epithelial cells, whereas γ-H2AX was completely absent (A). In normal bronchioli, iNOS expression was also found in smooth muscle cells (arrow; A). A clear increase in the coexpression of iNOS/p53/γ-H2AX was observed from hyperplastic (B and C) to dysplastic (D) bronchiolar cells. In tumors, colocalization was still present in some areas, although γ-H2AX levels were reduced compared to hyperplastic and advanced preneoplastic tissues (E and F). Counterstaining by Harris hematoxylin. Original magnifications, × 420 (C, E, and F); × 630 (A, B, and D).