Mutagenic Activity of a Mixture of Heterocyclic Amines at Doses below the Biological Threshold Level of Each

The combined mutagenic effects of six heterocyclic amines (Trp-P-1, Trp-P-2, Glu-P-1, Glu-P-2, MeIQ, and IQ) at doses below the biological threshold level of each were investigated in the reverse mutation assay with Salmonella typhimurium. The lowest mutagenic doses of heterocyclic amines in TA1978P (hisD3052, rfa/pKM101) were 40 to 200 times the lowest mutagenic doses in TA98 (hisD3052, rfa, uvrB/pKM101), a strain deficient in nucleotide excision repair. The six heterocyclic amines were mixed at doses below the biological threshold that were mutagenic to TA98 but not to TA1978P. A significant increase in the number of revertants in TA1978P was observed with combined heterocyclic amines. The results suggest that DNA adduct formation at doses below the biological threshold level was additive, with the total amount reflecting the mutagenicity. We should consider the potential for additive effects of mutagens when we consider biological thresholds, because most of environmental mutagens exist in complex mixtures of chemicals.

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