Ito N, Fukushima S, Tsuda H
Crit Rev Toxicol. 1985;15(2):109-50. doi: 10.3109/10408448509029322.
Carcinogenicity tests showed that addition of the antioxidant BHA to the diet of F344 rats induced high incidences of papilloma and squamous cell carcinoma of the forestomach of both sexes. Male hamsters given BHA for 24 weeks also developed papilloma showing downward growth into the submucosa of the forestomach. These results indicate that BHA should be classified in the category of "sufficient evidence of carcinogenicity" as judged by IARC criteria. The 3-tert isomer of BHA seemed to be responsible for the carcinogenicity of crude BHA in the forestomach of rats. BHT was not found to be carcinogenic in rats or mice. In two-stage carcinogenesis in rats after appropriate initiation, BHA enhanced carcinogenesis in the forestomach and urinary bladder of rats, but inhibited carcinogenesis in the liver. BHT enhanced the induction of urinary bladder tumors and inhibited that of liver tumors, but had no effect on carcinogenesis in the forestomach. BHT could be a promoter of thyroid carcinogenesis. Sodium L-ascorbate enhanced forestomach and urinary bladder carcinogenesis. Ethoxyquin enhanced kidney and urinary bladder carcinogenesis, but inhibited liver carcinogenesis. Thus, these antioxidants modify two-stage chemical carcinogenesis in the forestomach, liver, kidney, urinary bladder, and thyroid, but show organ-specific differences in effects.
致癌性试验表明，在F344大鼠的饮食中添加抗氧化剂丁基羟基茴香醚（BHA）会导致两性大鼠前胃乳头状瘤和鳞状细胞癌的高发病率。给予BHA 24周的雄性仓鼠也出现了乳头状瘤，且肿瘤向下生长至前胃黏膜下层。这些结果表明，根据国际癌症研究机构（IARC）的标准，BHA应被归类为“有充分致癌证据”的类别。BHA的3-叔丁基异构体似乎是粗制BHA对大鼠前胃致癌性的原因。没食子酸丙酯（BHT）在大鼠或小鼠中未发现有致癌性。在对大鼠进行适当启动后的两阶段致癌过程中，BHA增强了大鼠前胃和膀胱的致癌作用，但抑制了肝脏的致癌作用。BHT增强了膀胱肿瘤的诱导并抑制了肝脏肿瘤的诱导，但对前胃的致癌作用没有影响。BHT可能是甲状腺致癌的促进剂。L-抗坏血酸钠增强了前胃和膀胱的致癌作用。乙氧喹增强了肾脏和膀胱的致癌作用，但抑制了肝脏的致癌作用。因此，这些抗氧化剂会改变前胃、肝脏、肾脏、膀胱和甲状腺的两阶段化学致癌作用，但在作用上表现出器官特异性差异。
