Bleomycin damages DNA and causes lung injury and fibrosis. To determine whether 
bleomycin is associated with the appearance of DNA damage-inducible proteins, 
C3H mice received either 0.4 mg bleomycin or normal saline intratracheally and 
were killed 1 to 14 d later. The lungs were examined for expression of p53, 
p21(WAF1/PiCl), and proliferating cell nuclear antigen (PCNA) using 
immunohistochemistry and Western blotting. p53-positive cells first appeared at 
5 d after treatment and peaked at 7 d; PCNA-positive cells appeared at 1 d after 
treatment and peaked at 7 d; and p21-positive cells appeared at 5 d and peaked 
at 9 d. Western blot analysis confirmed that bleomycin upregulated the DNA 
damage-inducible proteins in a similar fashion. This is the first evidence that 
bleomycin causes a p53-dependent response associated with acute injury in the 
lung.