Morphometric analysis of irradiated rat lung: Modification by D-penicillamine

D-penicillamine (PEN), an inhibitor of collagen crosslinking, reduces radiation fibrosis in rat lung. To quantitate the effect of penicillamine on radiation-induced pulmonary histopathology, control-fed and PEN-treated (10 mg/day, p.o., continuously) rats were sacrificed 3, 6, 9, or 12 mo after a single dose of 25 Gy of /sup 60/Co γ-rays to the right hemithorax, or after sham-irradiation. Lung samples were stained with hematoxylin-eosin, and alveolar regions were analyzed by light microscopy for: total pulmonary cells (TPC)/mm/sup 2/, mast cells (MC)/mm/sup 2/, polymorphonuclear leucocytes (PMN)/mm/sup 2/, intraalveolar cells (IAC)/mm/sup 2/, mean alveolar diameter (Lm), and mean arterial wall thickness (MWT). In sham-irradiated rats, aging changes included decreased TPC/mm/sup 2/ and increased Lm. compared to controls, PEN-treated rats exhibited fewer IAC and PMN/mm/sup 2/ at all times after sham-irradiation. Two phases of response occurred in the irradiated lung. For the first 6 mo, there were increased TPC, MC, PMN, and IAC/mm/sup 2/, decreased Lm, and no change in MWT. From 6-12 mo after irradiation, all cell indices an Lm shifted toward, but did not reach normal values. In contrast, MWT increased greatly during that time. PEN ameliorated these responses at all times after irradiation, and was particularly effective in reducing the late increase in MWT