In Vivo Genotoxicity and Toxicity Assessment of Sterigmatocystin Individually and in Mixture with Aflatoxin B1

Abstract

Mycotoxins are natural food and feed contaminants produced by several molds. The primary mode of exposure in humans and animals is through mixtures. Aflatoxin B1 (AFB1) and sterigmatocystin (STER) are structurally related mycotoxins that share the same biosynthetic route. Few in vivo genotoxicity assays have been performed with STER. In the present genotoxicity study, Wistar rats were dosed orally with STER (20 mg/kg b.w.), AFB1 (0.25 mg/kg b.w.) or a mixture of both in an integrated micronucleus (bone marrow) and comet study (liver and kidney). STER was dosed at the highest feasible dose in corn oil. No increase in the percentage of micronuclei in bone marrow was observed at any condition. Slight DNA damage was detected in the livers of animals treated with AFB1 or the mixture (DNA strand breaks and Fpg (Formamidopyrimidine DNA glycosylase)-sensitive sites, respectively). Plasma, liver, and kidney samples were analyzed with LC-MS/MS demonstrating exposure to both mycotoxins. General toxicity parameters (organs absolute weight, biochemistry, and histopathology) were not altered either individually or in the mixture. The overall absence of individual genotoxicity did not allow us to set any type of interaction in the mixture. However, a possible toxicokinetic interaction was observed.

Keywords: aflatoxin B1; genotoxicity; in vivo; mixture; sterigmatocystin; toxicity.

Figure 1

AFB1 quantification of plasma (a) (ng/mL), liver (c), and kidney (e) samples (ng/g) at 3 h and 24 h. STER quantification of plasma (b) (ng/mL), liver (d), and kidney (f) samples (ng/g) for 3 h and 24 h. Dash lines LOQ: limit of quantification. Treatment groups were compared between 3 h and 24 h: (#) significant (p < 0.05) and (##) very significant (p < 0.01). Additionally, the groups of AFB1 or STER alone were compared to the mixture (3 h and 24 h separately): ($) significant (p < 0.05) and ($$) very significant (p < 0.01).