Age and dose-dependent accumulation of 4-hydroxynonenal in liver tissue.

Liver sections were stained with anti-4-hydroxy-2-nonenal (4-HNE) and hematoxylin counterstain as described in Materials and Methods. A. Bright-field images showing weak, moderate, or intense anti-4-HNE immunohistochemical staining. Scale bars  = 20 µm. B. Nuance renderings of images from Panel A (yellow, 4-HNE; blue, cell nuclei). C. Quantification of 4-HNE staining based on Nuance analysis. Box plot shows mean and interquartile ranges. Color denotes dose group. Values are normalized to 0 Gy, 250 day group. D. Plot showing correlation between actual and predicted natural logarithm (ln)-transformed 4-HNE values for HZE cohort. Predicted values are based on regression model incorporating age, dose, and dose-squared parameters. Each symbol represents one individual. Shape denotes age group; color denotes dose group using same values as in Panel B. E. Plot showing predicted 4-HNE values as a function of age and HZE dose. F, G. Same as Panels D, E for γ-ray cohorts. Regression model incorporates an age parameter only; dose parameters were non-significant.