Ki-ras mutation and cell proliferation of lung lesions induced by 1- nitropyrene in A/J mice

Feng Bai, Yoichi Nakanishi, Koichi Takayama, Xin Hai Pei, Hiroshi Tokiwa, Nobuyuki Hara

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of 1-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 (CGA) 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 1-NP-induced lung lesions in A/J mice.

Original languageEnglish
Pages (from-to)258-264
Number of pages7
JournalMolecular Carcinogenesis
Volume22
Issue number4
DOIs
Publication statusPublished - Aug 1 1998

Fingerprint

1-nitropyrene
Adenoma
Hyperplasia
Cell Proliferation
Lung
Mutation
Proliferating Cell Nuclear Antigen
Adenocarcinoma
Codon
ras Genes
Nucleolus Organizer Region
Silver Staining
Intraperitoneal Injections
Growth and Development
Point Mutation
Sequence Analysis
Arginine
Exons
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Ki-ras mutation and cell proliferation of lung lesions induced by 1- nitropyrene in A/J mice. / Bai, Feng; Nakanishi, Yoichi; Takayama, Koichi; Pei, Xin Hai; Tokiwa, Hiroshi; Hara, Nobuyuki.

In: Molecular Carcinogenesis, Vol. 22, No. 4, 01.08.1998, p. 258-264.

Research output: Contribution to journalArticle

Bai, Feng ; Nakanishi, Yoichi ; Takayama, Koichi ; Pei, Xin Hai ; Tokiwa, Hiroshi ; Hara, Nobuyuki. / Ki-ras mutation and cell proliferation of lung lesions induced by 1- nitropyrene in A/J mice. In: Molecular Carcinogenesis. 1998 ; Vol. 22, No. 4. pp. 258-264.
@article{2ffe3d566dc04d6cb6a68f22a4f1e534,
title = "Ki-ras mutation and cell proliferation of lung lesions induced by 1- nitropyrene in A/J mice",
abstract = "In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of 1-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 (CGA) 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 1-NP-induced lung lesions in A/J mice.",
author = "Feng Bai and Yoichi Nakanishi and Koichi Takayama and Pei, {Xin Hai} and Hiroshi Tokiwa and Nobuyuki Hara",
year = "1998",
month = "8",
day = "1",
doi = "10.1002/(SICI)1098-2744(199808)22:4<258::AID-MC7>3.0.CO;2-F",
language = "English",
volume = "22",
pages = "258--264",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Ki-ras mutation and cell proliferation of lung lesions induced by 1- nitropyrene in A/J mice

AU - Bai, Feng

AU - Nakanishi, Yoichi

AU - Takayama, Koichi

AU - Pei, Xin Hai

AU - Tokiwa, Hiroshi

AU - Hara, Nobuyuki

PY - 1998/8/1

Y1 - 1998/8/1

N2 - In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of 1-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 (CGA) 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 1-NP-induced lung lesions in A/J mice.

AB - In this study, lung lesions were found in male A/J mice 24 wk after intraperitoneal injection of 1-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 (CGA) 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 1-NP-induced lung lesions in A/J mice.

UR - http://www.scopus.com/inward/record.url?scp=0031857816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031857816&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2744(199808)22:4<258::AID-MC7>3.0.CO;2-F

DO - 10.1002/(SICI)1098-2744(199808)22:4<258::AID-MC7>3.0.CO;2-F

M3 - Article

VL - 22

SP - 258

EP - 264

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 4

ER -