Gunji Akemi, Uemura Akiko, Tsutsumi Masahiro, Nozaki Tadashige, Kusuoka Osamu, Omura Ken, Suzuki Hiroshi, Nakagama Hitoshi, Sugimura Takashi, Masutani Mitsuko
Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Cancer Lett. 2006 Sep 8;241(1):87-92. doi: 10.1016/j.canlet.2005.10.003. Epub 2005 Dec 9.
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.
在具有ICR/129Sv混合遗传背景的小鼠中,研究了聚(ADP-核糖)聚合酶-1(Parp-1)缺陷对4-硝基喹啉1-氧化物(4NQO)诱导致癌作用的影响。给Parp-1(+/+)、Parp-1(+/-)和Parp-1(-/-)的动物饮用含0.001% 4NQO的水32周,它们均出现了舌、腭和食管的乳头状瘤和鳞状细胞癌,但与Parp-1基因型无统计学上的显著差异。因此,Parp-1缺陷不会增加对导致大量DNA损伤的致癌物诱导致癌作用的易感性。该研究还表明,ICR/129Sv混合遗传背景与4NQO诱导食管肿瘤的高产率相关。