Abstract
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan-Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.
| Original language | English |
|---|---|
| Pages (from-to) | 284-289 |
| Number of pages | 6 |
| Journal | Lung Cancer |
| Volume | 65 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Sep 2009 |
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Keywords
- A/J mice
- Carcinogenesis
- Chemoprevention
- EGFR
- Gefitinib
- Pulmonary toxicity
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
- Cancer Research
Cite this
Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mice. / Kishino, Daizo; Kiura, Katsuyuki; Takigawa, Nagio; Katayama, Hideki; Kuyama, Shoichi; Sato, Ken; Okada, Toshiaki; Oohashi, Kadoaki; Tanimoto, Mitsune.
In: Lung Cancer, Vol. 65, No. 3, 09.2009, p. 284-289.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of gefitinib on N-nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mice
AU - Kishino, Daizo
AU - Kiura, Katsuyuki
AU - Takigawa, Nagio
AU - Katayama, Hideki
AU - Kuyama, Shoichi
AU - Sato, Ken
AU - Okada, Toshiaki
AU - Oohashi, Kadoaki
AU - Tanimoto, Mitsune
PY - 2009/9
Y1 - 2009/9
N2 - Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan-Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.
AB - Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan-Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.
KW - A/J mice
KW - Carcinogenesis
KW - Chemoprevention
KW - EGFR
KW - Gefitinib
KW - Pulmonary toxicity
UR - http://www.scopus.com/inward/record.url?scp=67651252080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651252080&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2008.11.021
DO - 10.1016/j.lungcan.2008.11.021
M3 - Article
VL - 65
SP - 284
EP - 289
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 3
ER -