Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts

Gunji, Akemi; Uemura, Akiko; Tsutsumi, Masahiro; Nozaki, Tadashige; Kusuoka, Osamu; Omura, Ken; Suzuki, Hiroshi; Nakagama, Hitoshi; Sugimura, Takashi; Masutani, Mitsuko

doi:10.1016/j.canlet.2005.10.003

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Volume 241, Issue 1 , Pages 87-92, 8 September 2006

Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts

Akemi Gunji
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
- Department of Oral Surgery, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan
Akiko Uemura
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
- ADP-ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Masahiro Tsutsumi
- Department of Oncological Pathology, Cancer Center, Nara Medical University, 840, Shijo-cho, Kashihara, Nara 634-8521, Japan
Tadashige Nozaki
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Osamu Kusuoka
- Department of Oncological Pathology, Cancer Center, Nara Medical University, 840, Shijo-cho, Kashihara, Nara 634-8521, Japan
Ken Omura
- Department of Oral Surgery, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan
- Department of Advanced Molecular Diagnosis and Maxillofacial Surgery, Hard Tissue Genome Research Center, Tokyo Medical and Dental University
Hiroshi Suzuki
- Chugai Pharmaceutical Co. Ltd. Gotemba, 1-135, Komakado, Gotemba, Shizuoka, 412-0038, Japan
Hitoshi Nakagama
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Takashi Sugimura
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Mitsuko Masutani
- Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
- ADP-ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
- Corresponding author. Address: ADP-ribosylation in Oncology Project, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. Tel.: +81 3 3542 2511x4551; fax: +81 3 3542 2530.

Received 28 July 2005; received in revised form 2 October 2005; accepted 7 October 2005.

Abstract

The impact of poly(ADP-ribose) polymerase-1 (Parp−1)-deficiency on 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis was studied in mice with an ICR/129Sv mixed genetic background. Parp-1^+/+, Parp−1^+/− and Parp-1^−/− animals given 4NQO for thirty-two weeks at 0.001% in their drinking water developed papillomas and squamous cell carcinomas of the tongue, palate and esophagus, but with no statistically significant variation with the Parp−1 genotype. Thus Parp-1 deficiency does not elevate susceptibility to carcinogenesis induced by a carcinogen which gives rise to bulky DNA lesions. This study also indicated that the ICR/129Sv mixed genetic background is associated with high yield induction of esophageal tumors by 4NQO.

Keywords: 4-Nitroquinoline 1-oxide, Poly(ADP-ribose) polymerase-1, Squamous cell carcinoma, Carcinogenesis, Knockout mice