First Author | Bai F | Year | 1998 |
Journal | Mol Carcinog | Volume | 22 |
Issue | 4 | Pages | 258-64 |
PubMed ID | 9726818 | Mgi Jnum | J:49725 |
Mgi Id | MGI:1278057 | Doi | 10.1002/(sici)1098-2744(199808)22:4<258::aid-mc7>3.0.co;2-f |
Citation | Bai F, et al. (1998) Ki-ras mutation and cell proliferation of lung lesions induced by 1-nitropyrene in A/J mice. Mol Carcinog 22(4):258-64 |
abstractText | In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of l-nitropyrene (1- NP). The lesions were classified into three categories: alveolar/bronchiolar hyperplasia, adenoma, and adenocarcinoma. The proliferation kinetics of cells in the lesions were evaluated by assessing proliferating cell nuclear antigen (PCNA) expression and silver-staining nucleolar organizer regions (AgNORs). Furthermore, the role of the Ki-ras gene in tumorigenesis was studied by detecting point mutations in Ki-ras codons 12, 13, and 61 by polymerase chain reaction and sequence analysis. The PCNA-positive rates (+/- standard deviations) in various samples were as follows: 0% for specimens from six untreated animals and six uninvolved areas, 4.26 +/- 3.94% for 19 hyperplasias (hyperplasias vs normal lung tissue, P < 0.01), 13.24 +/- 6.35% for 25 adenomas (adenomas vs hyperplasias, P < 0.01), and 38.0 +/- 9.63% for four adenocarcinomas (adenocarcinomas vs adenomas, P < 0.01). The corresponding mean AgNOR scores were as follows: 1.10 +/- 0.05 for the untreated animals, 1.32 +/- 0.09 for the uninvolved areas, 1.72 +/- 0.59 for the hyperplasias (hyperplasias vs normal lung tissue, P > 0.05), 2.74 +/- 0.70 for the adenomas (adenomas vs hyperplasias, P < 0.01), and 5.22 +/- 0.62 for the adenocarcinomas (adenocarcinomas vs adenomas, P < 0.01). Ki-ras gene mutations were identified in three of four (75%) adenocarcinomas, six of 23 (26%) adenomas, and two of 17 (12%) hyperplasias. No mutations were found in normal lung tissue. The most frequent Ki-ras mutation was an arginine (CCA) AT --> GC transition at codon 61 in exon 2. The PCNA- positive rates and AgNOR scores of cases with Ki-ras mutations were higher than those without an identified mutation (P < 0.05). Ki-ras mutations at codon 61 (Arg) may therefore influence the growth or development of l-NP- induced lung lesions in A/J mice. Mol. Carcinog. 22:258- 264, 1998. (C) 1998 Wiley-Liss. Inc. |