Solvent-Mutagen Interactions in the Salmonella/Microsome Assay


Abstract

The Salmonella/microsome assay is the most used test for assessing the mutagenic potential of chemicals and/or their metabolites. A modified Salmonella assay has also been employed to evaluate antimutagenic activities of natural and synthetic substances. Although several solvents used for testing water insoluble compounds are regarded as compatible with the assay, so far their effects on the mutagenic response have not been systematically studied. This study was conducted to investigate the effects of dimethylsulfoxide (DMSO), ethanol (EtOH) and acetone (ACE) on the Salmonella/ microsome assay sensitivity to detect a set of mutagens generally used as positive controls. Non-toxic doses of solvents (0, 12.5, 25, 50 and 100 μl/plate) were tested against non-toxic doses of mutagens with a sensitive tester strain without (TA100: SA; TA98: NPD and 2-NF; TA97a: 4-NQNO) and with (TA98:AFB1, B[a]P and 2-AF; TA1535: CP) a rat liver S9 mixture. Results showed that the solvents did not alter the effects of direct acting mutagens except for an EtOH-induced nearly 30% enhancement of SA mutagenicity. Nonetheless, EtOH, ACE and to a lesser extent DMSO attenuated the effects of most tested promutagens. The foregoing findings suggested that the solvents impaired the conversion of promutagens into their active metabolites by the rat liver S9. The mode by which solvents interfered with the extrinsic metabolic activation system, however, remains unclear.

Keywords

Antimutagenic Agents, Salmonella typhimurium, Ethanol, Acetone, Dimethylsulfoxide.

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