Nakae D, Kotake Y, Kishida H, Hensley K L, Denda A, Kobayashi Y, Kitayama W, Tsujiuchi T, Sang H, Stewart C A, Tabatabaie T, Floyd R A, Konishi Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Cancer Res. 1998 Oct 15;58(20):4548-51.
Male Wistar rats were fed a choline-deficient, L-amino acid-defined (CDAA) diet alone or in combination with a nitrone-based free radical trapping agent, phenyl N-tert-butyl nitrone (PBN) in the drinking water at the concentrations of 0.013, 0.065, and 0.130% for 12 weeks. PBN inhibited the changes that are normally induced in the livers of rats by the CDAA diet feeding, i.e., development of putative preneoplastic lesions, proliferation of connective tissue, reduction of glutathione S-transferase activity, formation of 8-hydroxyguanine in DNA, and an increase in inducible cyclo-oxygenase (COX2) activity. PBN, however, did not prevent the increases in the COX2 mRNA or protein levels brought on by the CDAA diet These results indicate that the loss of glutathione S-transferase activity and COX2 induction may play significant roles in rat liver carcinogenesis by the CDAA diet and that PBN prevents neoplasia not only by its radical scavenging activity but also by inhibiting COX2 activity at the catalytic level.
雄性Wistar大鼠单独喂食胆碱缺乏、L-氨基酸限定（CDAA）饮食，或与饮用水中浓度为0.013%、0.065%和0.130%的基于硝酮的自由基捕获剂苯基N-叔丁基硝酮（PBN）联合喂食12周。PBN抑制了CDAA饮食喂养正常诱导大鼠肝脏发生的变化，即假定的癌前病变的发展、结缔组织的增殖、谷胱甘肽S-转移酶活性的降低、DNA中8-羟基鸟嘌呤的形成以及诱导型环氧化酶（COX2）活性的增加。然而，PBN并未阻止CDAA饮食引起的COX2 mRNA或蛋白质水平的升高。这些结果表明，谷胱甘肽S-转移酶活性的丧失和COX2的诱导可能在CDAA饮食诱导的大鼠肝癌发生中起重要作用，并且PBN不仅通过其自由基清除活性，还通过在催化水平抑制COX2活性来预防肿瘤形成。
