Enhanced inhibition of viral interferon induction by bioactivated aflatoxins

Abstract

The inhibitory magnitude of aflatoxins of the B and G series, enzy‐matically bioactivated by rat liver (S9) homogenate, on interferon‐α/β induction by influenza virus in rhesus monkey kidney (LLC‐MK₂) cell monolayers was studied. Inhibition of interferon induction followed a structure‐activity series with decreasing potency in the order aflatoxin B₁ > G₁ > B₂ > G₂ 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 alone. 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 Sendai virus growth were attained in nonactivated and bioactiyated aflatoxins (B₁ and G₂)‐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 they were bioactivated or not. The data indicate that bioactivating aflatoxins, presumably through reactive metabolites, enhances their capability to inhibit viral induction of interferon‐α/β significantly. The overall findings are discussed in relation to possible mechanisms involved.

Notes

Please direct all correspondence to Dr. Nicholas Hahon, National Institutte of Occupational Safety and Health ‐ ALOSH, 944 Chestnut Ridge Road, Morgantown, WV 26505–2888.