Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response.
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.
Mishra
A
A
Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Doyle
N A
NA
Martin WJ 2cnd
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D015151:Immunoblotting; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin