Hirose M, Ozaki K, Takaba K, Fukushima S, Shirai T, Ito N
First Department of Pathology, Nagoya City University Medical School, Japan.
Carcinogenesis. 1991 Oct;12(10):1917-21. doi: 10.1093/carcin/12.10.1917.
The modifying effects of the naturally occurring antioxidants gamma-oryzanol, phytic acid, tannic acid and n-tritriacontane-16, 18-dione (TTAD) were investigated in a rat wide-spectrum organ carcinogenesis model. Animals were initiated with two i.p. injections of 1000 mg/kg body wt 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) followed by two i.g. administrations of 1500 mg/kg body wt N-ethyl-N-hydroxy-ethylnitrosamine (EHEN), and then three s.c. injections of 75 mg/kg body wt 3,2'-dimethyl-4-aminobiphenyl (DMAB) during the first 3 weeks. Starting 1 week after the last injection, groups of rats received diet containing 1% gamma-oryzanol, 2% phytic acid, 0.2% TTAD or 1% tannic acid or basal diet alone for 32 weeks. Animals were then killed and complete autopsy was performed at the end of week 36. Histological examination revealed enhancement of lung carcinogenesis by gamma-oryzanol, and the incidence of urinary bladder papillomas to be increased by phytic acid. On the other hand, TTAD inhibited hepatic and pancreatic carcinogenesis. Phytic acid and tannic acid were marginally effective in inhibiting hepatic and colon carcinogenesis respectively. The results thus indicated that naturally occurring antioxidants each exert specific modifying effects depending on the organ site and indicate that wide-spectrum carcinogenesis models are useful for defining complex influences.
在大鼠广谱器官致癌模型中研究了天然抗氧化剂γ-谷维素、植酸、单宁酸和正三十三烷-16,18-二酮(TTAD)的修饰作用。动物通过腹腔注射两次1000mg/kg体重的2,2'-二羟基二正丙基亚硝胺(DHPN)启动,随后经口给予两次1500mg/kg体重的N-乙基-N-羟乙基亚硝胺(EHEN),然后在最初3周内皮下注射三次75mg/kg体重的3,2'-二甲基-4-氨基联苯(DMAB)。在最后一次注射后1周开始,每组大鼠接受含1%γ-谷维素、2%植酸、0.2%TTAD或1%单宁酸的饮食或仅接受基础饮食,持续32周。然后在第36周结束时处死动物并进行完整尸检。组织学检查显示γ-谷维素增强了肺癌发生,植酸增加了膀胱乳头状瘤的发生率。另一方面,TTAD抑制了肝癌和胰腺癌的发生。植酸和单宁酸分别对抑制肝癌和结肠癌的发生有轻微效果。因此,结果表明天然抗氧化剂各自根据器官部位发挥特定的修饰作用,并表明广谱致癌模型对于确定复杂影响是有用的。