生物活化黄曲霉毒素对病毒干扰素诱生的抑制作用

Enhanced Inhibition of Viral Interferon Induction by Bioactivated Aflatoxins

用鼠肝匀浆(S_9)代谢活化黄曲霉毒素B族和G族,研究它们对流感病毒在恒河猴肾细胞(LLC-MK_2)诱导干扰素-α/β的抑制作用。结果显示活化与未活化的黄曲霉毒素对干扰素诱生都有抑制作用。但代谢活化后,抑制作用增强,抑制作用的大小按B_1>G_1>B_2>G_2顺序排列,显示有结构-活性关系。而干扰素赋予细胞的抗病毒能力并不受黄曲霉毒素的影响。

The inhibitory magnitude of aflatoxins of the B and G series, enzymatieally bioactivated by rat liver (S_9) homogenate,on interferon-α/β induction by influenza virus in rhesus monkey kindney (LLC-MK,) cell monolayers was studied. Inhibition of interferon induction followed a structure-activity series with decreasing potency in the order aflatoxin B_1>G_1>B_2>G_2 by both nonactivated and bioactivated aflatoxins. The quantity of bioactivated aflatoxin of all types required to achieve 50% inhibition of interferon induction was fourfold less than that of aflatoxins per se. Dose-response relationships between aflatoxin quantity and interferon inhibition were evident under all conditions relative to aflatoxin type and bioactivation status. That higher levels of Sendal virus growth were attained in nonaetivated and bioactivated aflatoxins (B_1 and G_2)-pretreated cells than in untreated cell monolayers was related to decreased production of interferon by aflatoxins. The ability of interferon to confer cellular resistance against viral infection, however,was not impaired by aflatoxins whether or not they were bioactivated. The data indicate that bioactivation of aflatoxins,presumably through reactive metabolites,enhances their capa bility of inhibiting viral induction of interferon-α/β significantly more than nonactivated aflatoxins. The overall findings are discussed in relation to possible mechanisms involved.