Influence of benzoflavone on aflatoxin B1-induced cytotoxicity, mutation, and transformation of C3H/10T1/2 cells.

Influence of benzoflavone on aflatoxin B1-induced cytotoxicity, mutation, and transformation of C3H/10T1/2 cells.
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发表时间:
1983-06
期刊:
影响因子:
11.2
通讯作者:
P. Billings;A. Uwaifo;C. Heidelberger
P. Billings;A. Uwaifo;C. Heidelberger
中科院分区:
医学1区
文献类型:
--
作者:
P. Billings;A. Uwaifo;C. Heidelberger

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黄曲霉毒素B1 (AFLB1)是真菌黄曲霉的代谢物,在几种动物中具有肝毒性和致癌性,被认为在人类肝癌中起病因学作用。C3H/10T1/2克隆8只小鼠胚胎成纤维细胞被aflb1杀死、突变和形态转化。7,8-苯黄酮是一种已知的芳烃羟化酶抑制剂,在C3H/10T1/2细胞中抑制这种酶的活性。此外,苯甲黄酮抑制AFLB1与C3H/10T1/2细胞DNA的结合。苯甲黄酮还能抑制AFLB1诱导的C3H/10T1/2细胞的细胞毒性和突变,并抑制AFLB1活化成诱变代谢物,使Ames沙门氏菌测试菌株TA98恢复。有趣的是,苯并黄酮对AFLB1对这些细胞的致癌转化没有影响。因此,苯甲黄酮抑制AFLB1的DNA结合、细胞毒性和诱变作用,但不降低该真菌毒素对C3H/10T1/2细胞的形态转化。
Aflatoxin B1 (AFLB1), a metabolite of the fungus Aspergillus flavus, is hepatotoxic and hepatocarcinogenic in several animal species and is thought to play an etiological role in human liver cancer. C3H/10T1/2 clone 8 mouse embryo fibroblasts are killed, mutated, and morphologically transformed byAFLB1. 7,8-Benzoflavone, a known inhibitor of aryl hydrocarbon hydroxylase, inhibits this enzymatic activity in C3H/10T1/2 cells. Furthermore, benzoflavone inhibits the binding of AFLB1, to the DNA of C3H/10T1/2 cells. Benzoflavone also inhibits AFLB1-induced cytotoxicity and mutation of C3H/10T1/2 cells, as well as inhibiting the activation of AFLB1 into mutagenic metabolites capable of reverting the Ames Salmonella tester strain TA98. Interestingly, benzoflavone had no effect on the oncogenic transformation of these cells by AFLB1. Therefore, benzoflavone inhibits the DNA binding, cytotoxic, and mutagenic effects of AFLB1 but does not reduce the morphological transformation of C3H/10T1/2 cells by this mycotoxin.