Toxicity and Biochemical and Fine Structural Effects of Synthetic Aflatoxins M₁ and B₁ in Rat Liver

Summary

Synthetic, racemic aflatoxins M₁ and B₁ were lethal to male Fischer rats at a single dose of 1.5 mg/kg but caused only transient weight loss at lower doses. Aflatoxin B₁ of natural origin (nonracemic) was lethal at doses of 0.6 mg/kg and higher. When administered at a dose of 1.0 mg/kg, both synthetic toxins suppressed precursor incorporation into liver nuclear RNA. Twelve hours after toxin administration, M₁ inhibited incorporation by 80% and B₁ by 65%. Under comparable conditions, natural B₁ caused 85% inhibition at a dose of 0.5 mg/kg. These effects were accompanied by proportionate decreases in nuclear RNA/DNA ratios. Fine structural changes induced in liver parenchymal cells by the synthetic, racemic toxins at 1.0 mg/kg were indistinguishable from those caused by natural B₁ at a dose of 0.5 mg/kg. Principal alterations consisted of macrosegregation of nucleolar components, proliferation of smooth endoplasmic reticulum, disorganization of rough endoplasmic reticulum, and dissociation of ribosomes from ergastoplasmic membranes. These findings indicated that aflatoxins M₁ and B₁ caused qualitatively similar acute effects in the rat and seemed to be approximately equal in potency. If so, only one isomer in the racemic mixture of the synthetic compounds may be active.