Ito N, Hirose M, Fukushima S, Tsuda H, Tatematsu M, Asamoto M
Toxicol Pathol. 1986;14(3):315-23. doi: 10.1177/019262338601400305.
Studies were made on the carcinogenic activity of butylated hydroxyanisole (BHA) in rats, mice, and hamsters and the effect of the antioxidants BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), sodium L-ascorbate (SA), ascorbic acid (AA), sodium erythorbate (SE), propyl gallate (PG), and alpha-tocopherol, on two-stage chemical carcinogenesis in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1,2-dimethylhydrazine (DMH), diethylnitrosamine (DEN), 7,12-dimethylbenz(a)anthracene (DMBA), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-hydroxyethylnitrosamine (EHEN), or N-methylnitrosourea (MNU). BHA clearly induced squamous cell carcinomas in both the rat and hamster forestomach. The tumorigenic action of crude BHA on the forestomach is largely due to 3-tert-BHA. In two-stage chemical carcinogenesis, BHA promoted MNNG or MNU-initiated forestomach and BBN- or MNU-initiated urinary bladder carcinogenesis and inhibited DEN- or EHEN-initiated liver and DMBA-initiated mammary carcinogenesis. BHT demonstrated promotion potential for urinary bladder and MNU-initiated thyroid carcinogenesis and inhibited DMBA-initiated ear duct carcinogenesis. EQ promoted EHEN-initiated kidney carcinogenesis and inhibited DMBA-initiated mammary and EHEN-initiated liver carcinogenesis. SA promoted forestomach and urinary bladder carcinogenesis and SE likewise enhanced urinary bladder carcinogenesis. alpha-Tocopherol inhibited ear duct carcinogenesis. No effects of any of the antioxidants on glandular stomach carcinogenesis were found. The results clearly demonstrated that antioxidants have different effects (promoting or inhibitory influences) depending on the organ studied and suggest the importance of a whole body approach to their investigation.
对叔丁基羟基茴香醚（BHA）在大鼠、小鼠和仓鼠中的致癌活性以及抗氧化剂BHA、二丁基羟基甲苯（BHT）、乙氧喹（EQ）、L-抗坏血酸钠（SA）、抗坏血酸（AA）、异抗坏血酸钠（SE）、没食子酸丙酯（PG）和α-生育酚对用N-甲基-N'-硝基-N-亚硝基胍（MNNG）、1,2-二甲基肼（DMH）、二乙基亚硝胺（DEN）、7,12-二甲基苯并(a)蒽（DMBA）、N-丁基-N-(4-羟基丁基)亚硝胺（BBN）、N-乙基-N-羟乙基亚硝胺（EHEN）或N-甲基亚硝基脲（MNU）引发的大鼠两阶段化学致癌作用的影响进行了研究。BHA在大鼠和仓鼠的前胃中均明显诱发了鳞状细胞癌。粗制BHA对前胃的致瘤作用主要归因于3-叔丁基-BHA。在两阶段化学致癌过程中，BHA促进了MNNG或MNU引发的前胃癌以及BBN或MNU引发的膀胱癌发生，并抑制了DEN或EHEN引发的肝癌和DMBA引发的乳腺癌发生。BHT显示出对膀胱癌和MNU引发的甲状腺癌的促进潜力，并抑制了DMBA引发的耳道癌发生。EQ促进了EHEN引发的肾癌发生，并抑制了DMBA引发的乳腺癌和EHEN引发的肝癌发生。SA促进了前胃癌和膀胱癌发生，SE同样增强了膀胱癌发生。α-生育酚抑制了耳道癌发生。未发现任何一种抗氧化剂对腺胃癌发生有影响。结果清楚地表明，抗氧化剂根据所研究的器官具有不同的作用（促进或抑制作用），并提示采用全身方法进行研究的重要性。
