Point mutation of K-ras gene in cisplatin-induced lung tumours in A/J mice

Akiko Hisamoto, Eisei Kondo, Katsuyuki Kiura, Toshiaki Okada, Shinobu Hosokawa, Junko Mimoto, Nagio Takigawa, Masahiro Tabata, Mitsune Tanimoto

Research output: Contribution to journalArticle

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Abstract

The risks of secondary lung cancer in patients with early stage non-small and small cell lung cancers are estimated to be 1-2% and 2-10% per patient per year, respectively. Surprisingly, the incidence of second primary cancer in locally advanced non-small cell lung cancer at 10 years, following cisplatin-based chemotherapy with concurrent radiotherapy, increases to 61%. Those patients, on the road to being cured, cannot overlook the possibility of developing a second primary cancer. We developed a second primary lung cancer model using cisplatin as a carcinogen in A/J mice to screen for chemopreventive agents for a second malignancy. In the primary lung tumour model, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo(a)pyrene (BaP), urethane induces specific K-ras mutations in codon 12, codon 12, and codon 61, respectively, in the A/J mice. In this study, we investigated the mechanisms of carcinogenicity by cisplatin in the A/J mice. In the cisplatin-induced tumours, we found no K-ras codon 12 mutation, which is the major mutation induced by NNK or BaP. K-ras gene mutations in codon 13 and codon 61 were found in one tumour (4%) and five tumours (17.8%), respectively. These findings suggest that cisplatin is partially related to K-ras codon 61 mutations, and that the mechanism of carcinogenicity by cisplatin is different from that by NNK or BaP.

Original languageEnglish
Pages (from-to)15-20
Number of pages6
JournalLung Cancer
Volume58
Issue number1
DOIs
Publication statusPublished - Oct 2007

Fingerprint

ras Genes
Point Mutation
Codon
Cisplatin
Second Primary Neoplasms
Lung
Benzo(a)pyrene
Mutation
Neoplasms
Lung Neoplasms
Butanones
Urethane
Small Cell Lung Carcinoma
Non-Small Cell Lung Carcinoma
Carcinogens
Radiotherapy
Drug Therapy
Incidence

Keywords

  • A/J mouse
  • Cisplatin
  • K-ras mutation
  • Second primary cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Hisamoto, A., Kondo, E., Kiura, K., Okada, T., Hosokawa, S., Mimoto, J., ... Tanimoto, M. (2007). Point mutation of K-ras gene in cisplatin-induced lung tumours in A/J mice. Lung Cancer, 58(1), 15-20. https://doi.org/10.1016/j.lungcan.2007.05.012

Point mutation of K-ras gene in cisplatin-induced lung tumours in A/J mice. / Hisamoto, Akiko; Kondo, Eisei; Kiura, Katsuyuki; Okada, Toshiaki; Hosokawa, Shinobu; Mimoto, Junko; Takigawa, Nagio; Tabata, Masahiro; Tanimoto, Mitsune.

In: Lung Cancer, Vol. 58, No. 1, 10.2007, p. 15-20.

Research output: Contribution to journalArticle

Hisamoto, A, Kondo, E, Kiura, K, Okada, T, Hosokawa, S, Mimoto, J, Takigawa, N, Tabata, M & Tanimoto, M 2007, 'Point mutation of K-ras gene in cisplatin-induced lung tumours in A/J mice', Lung Cancer, vol. 58, no. 1, pp. 15-20. https://doi.org/10.1016/j.lungcan.2007.05.012
Hisamoto, Akiko ; Kondo, Eisei ; Kiura, Katsuyuki ; Okada, Toshiaki ; Hosokawa, Shinobu ; Mimoto, Junko ; Takigawa, Nagio ; Tabata, Masahiro ; Tanimoto, Mitsune. / Point mutation of K-ras gene in cisplatin-induced lung tumours in A/J mice. In: Lung Cancer. 2007 ; Vol. 58, No. 1. pp. 15-20.
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