Goeger D E, Shelton D W, Hendricks J D, Pereira C, Bailey G S
Department of Food Science and Technology, Oregon State University, Corvallis 97331.
Carcinogenesis. 1988 Oct;9(10):1793-800. doi: 10.1093/carcin/9.10.1793.
Butylated hydroxyanisole (BHA) and beta-naphthoflavone (BNF), both chemicals with anti-carcinogenic properties in some experimental animals, were compared for effects on aflatoxin B1 (AFB1) metabolism, hepatic DNA adduct formation and carcinogenesis in the rainbow trout. Dietary BHA had no effect on the hepatic tumor incidence when fed at 0.03 or 0.3% 4 weeks prior to and during a 4 week dietary exposure of 10 p.p.b. AFB1. BNF, when fed at 0.005 or 0.05% under similar conditions, significantly reduced tumor response, which confirms previous results in trout (Nixon et al., Carcinogenesis, 5, 615-619, 1984). BHA fed at either 0.03 or 0.3% for 8 weeks had no post-initiation effect on the 52 week hepatic tumor incidence of trout exposed to a 0.5 p.p.m. AFB1 solution as embryos. A similar post-initiation exposure to 0.05% BNF significantly enhanced AFB1 tumor response. The influence of dietary BHA and BNF on AFB1 metabolism and DNA adduct formation and persistence in trout were examined. A 3 week pre-treatment with 0.3% dietary BHA had no effect on in vivo hepatic nuclear AFB1-DNA adduct formation at 0.5, 1, 2 and 7 days after AFB1 i.p. injection. By contrast 0.05% dietary BNF reduced hepatic AFB1-DNA adducts to 33-60% of control levels at 0.5, 1, 2 and 4 days after AFB1 exposure. This was accompanied by significantly lower blood and liver levels of AFB1 during the first 24 h after i.p. injection. Livers of BNF trout also contained 4-fold more of the less carcinogenic metabolite, aflatoxin M1, and 50% less aflatoxicol (AFL), a metabolite with similar carcinogenicity as AFB1. Bile AFL-glucuronide levels were significantly decreased in BNF-fed trout, but total bile glucuronides were significantly increased due to a 15-fold increase in aflatoxicol-M1 glucuronide. Freshly isolated hepatocytes from BHA-fed fish, when incubated with AFB1 for 1 h, showed no difference in levels of AFB1-DNA adducts or ratios of AFB1 metabolites when compared to hepatocytes isolated from fish fed a control diet only. By contrast, dietary BNF has been previously shown to greatly enhance AFM1 production, reduce AFL production, and significantly reduce AFB1-DNA adduct formation in isolated trout hepatocytes (Bailey et al., Natl. Cancer Inst. Monograph, 65, 379-385, 1984). These results indicate that dietary BHA up to 0.3% does not alter AFB1 metabolism or DNA adduction in trout, nor does it inhibit or promote AFB1 hepatocarcinogenesis in this species.(ABSTRACT TRUNCATED AT 400 WORDS)
丁基羟基茴香醚（BHA）和β-萘黄酮（BNF）在一些实验动物中均具有抗癌特性，本研究比较了它们对虹鳟鱼体内黄曲霉毒素B1（AFB1）代谢、肝脏DNA加合物形成及致癌作用的影响。在虹鳟鱼4周的10 ppb AFB1饲料暴露期之前及期间，以0.03%或0.3%的剂量投喂BHA，对肝脏肿瘤发生率没有影响。在类似条件下，以0.005%或0.05%的剂量投喂BNF，显著降低了肿瘤反应，这证实了之前在鳟鱼中的研究结果（尼克松等人，《癌变》，第5卷，615 - 619页，1984年）。在胚胎期接触0.5 ppm AFB1溶液的虹鳟鱼，在之后52周的肝脏肿瘤发生率方面，以0.03%或0.3%的剂量投喂BHA 8周，对启动后的肿瘤发生率没有影响。类似地，启动后接触0.05%的BNF显著增强了AFB1诱导的肿瘤反应。研究了饲料中BHA和BNF对虹鳟鱼体内AFB1代谢、DNA加合物形成及持久性的影响。在AFB1腹腔注射后0.5、1、2和7天，用0.3%的饲料BHA进行3周预处理，对体内肝脏细胞核AFB1 - DNA加合物的形成没有影响。相比之下，在AFB1暴露后0.5、1、2和4天，0.05%的饲料BNF可将肝脏AFB1 - DNA加合物水平降至对照水平的33% - 60%。这伴随着腹腔注射后最初24小时内血液和肝脏中AFB1水平的显著降低。BNF处理的鳟鱼肝脏中，致癌性较低的代谢产物黄曲霉毒素M1含量多4倍，而与AFB1致癌性相似的代谢产物黄曲霉毒素醇（AFL）含量少50%。在BNF喂养的鳟鱼中，胆汁AFL - 葡萄糖醛酸苷水平显著降低，但由于黄曲霉毒素醇 - M1葡萄糖醛酸苷增加15倍，总胆汁葡萄糖醛酸苷显著增加。与仅喂食对照饲料的鱼分离的肝细胞相比，用AFB1孵育1小时后，从喂食BHA的鱼中新鲜分离的肝细胞在AFB1 - DNA加合物水平或AFB1代谢产物比例上没有差异。相比之下，之前的研究表明，饲料BNF可极大地增强AFM1的产生，减少AFL的产生，并显著减少分离的鳟鱼肝细胞中AFB1 - DNA加合物的形成（贝利等人，《国家癌症研究所专论》，第65卷，379 - 385页，1984年）。这些结果表明，高达0.3%的饲料BHA不会改变虹鳟鱼体内AFB1的代谢或DNA加合作用，也不会抑制或促进该物种中AFB1诱导的肝癌发生。（摘要截选至400字）
