Association of p53, K-ras and proliferating cell nuclear antigen with rat lung lesions following exposure to simulated nuclear fuel particles.
Expression of p53, K-ras, and proliferating cell nuclear antigen (PCNA) and mutations of p53 and K-ras genes in lung lesions of Han/Wistar rats were investigated by immunohistochemistry and direct DNA sequencing following a long-term exposure of animals to neutron-activated UO2 particles. The p53 protein was overexpressed in all five malignant tumors, in 62% of benign tumors, and in 42% of hyperplastic lesions examined. K-ras protein and PCNA levels were only slightly elevated in all types of lung lesions. In three malignant tumors a C-->T transition was detected in codon 288 (human 290) of the p53 gene, but this mutation was not present in seven other tumors analyzed. No mutations were detected in codons 12/13 and 61 of the K-ras gene in any of the five tumors analyzed. Our findings suggest that K-ras overexpression is a rare alteration, whereas p53 protein overexpression (sometimes associated with mutated p53 gene), as assessed with the CM5 antibody, is a relatively common phenomenon in hot particle-induced preneoplastic and neoplastic rat lung lesions.
Kosma
V M
VM
Department of Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland.
Lang
P S
PS
Servomaa
M K
MK
Leszczynski
D
D
Rytömaa
T J
TJ
D000818:Animals; D004273:DNA, Neoplasm / Q000235:genetics; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics; D017974:Uranium Compounds / Q000009:adverse effects*
D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D017974:Uranium Compounds; D016283:Proto-Oncogene Proteins p21(ras); C012597:uranium dioxide