Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential

Abstract

Aflatoxins and their animal biotransformation products were screened for carcinogenic potential using the Ames' in vitro microbial detection system for carcinogens as bacterial mutagens [B. N. Ames et al. (1973) Proc. Natl. Acad. Sci. USA 70,2281-2285]. Aflatoxicol, aflatoxins G1 and M1, aflatoxicol H1, and aflatoxins Q1, B2, P1, G2, B2a, and G2a, listed in order of decreasing mutagenic potency, were all less active than aflatoxin B1. No compound possesses activity in the absence of the rat liver preparation, and this indicates none of the animal metabolites are the ultimate mutagenic and/or carcinogenic species. The relative mutagenic potency observed with this in vitro system qualitatively correlates with in vivo carcinogenic data. Comparison of both methods indicates: (i) aflatoxin B1 possessed the structure optimal for both mutagenicity and carcinogenicity, (ii) the decreased carcinogenicity of various animal metabolites is associated with their decreased mutagenicity, and (iii) the 2,3-double bond is involved in both the mutagenic and carcinogenic activity of aflatoxins. The Ames' assay has been demonstrated to be an extremely promising (toxicological) tool for the analysis of mycotoxins for mutagenic and/or carcinogenic activity.