Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) co-existed in food and water, and were associated with hepatocellular carcinoma (HCC). AFB1 induced HCC by activating oxidative stress and generating AFB1-DNA adducts, while MC-LR could promote HCC progression. However, whether they have co-effects in HCC progression remains uncertain. In this study, we found the antagonistic effects of MC-LR on AFB1 induced HCC when they were exposed simultaneously. Compared with single exposure to AFB1, co-exposed to MC-LR significantly repressed the AFB1 induced malignant transformation of human hepatic cells and the glutathione S-transferase Pi positive foci formation in rat livers. MC-LR inhibited AFB1 induced upregulation of cytochrome P450 family 1 subfamily A member 2 (CYP1A2) and reduced the AFB1-DNA adducts generation in both human hepatic cells and rat livers. These results suggest that when co-exposure with AFB1, MC-LR might repress hepatocarcinogenicity of AFB1, which might be associated with its repression on AFB1 induced CYP1A2 upregulation and activation.

中文翻译：

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低剂量微囊藻毒素-LR通过降低细胞色素P450 1A2表达和黄曲霉毒素B1-DNA加合物生成来拮抗黄曲霉毒素B1诱导的肝癌发生。

黄曲霉毒素B1（AFB1）和微囊藻毒素LR（MC-LR）在食物和水中共存，并与肝细胞癌（HCC）相关。AFB1通过激活氧化应激并产生AFB1-DNA加合物来诱导HCC，而MC-LR可以促进HCC的进展。但是，它们是否对肝癌的进展有共同作用仍不确定。在这项研究中，我们发现MC-LR同时暴露于AFB1诱导的HCC具有拮抗作用。与单次暴露于AFB1相比，与MC-LR共同暴露可显着抑制AFB1诱导的人肝细胞恶性转化和大鼠肝脏中谷胱甘肽S-转移酶Pi阳性灶的形成。MC-LR抑制了AFB1诱导的细胞色素P450家族1亚家族A成员2（CYP1A2）的上调，并减少了人肝细胞和大鼠肝脏中AFB1-DNA加合物的生成。这些结果表明，与AFB1共同暴露时，MC-LR可能会抑制AFB1的肝致癌性，这可能与其抑制AFB1诱导的CYP1A2上调和激活有关。