Mutation Spectra of the Drinking Water Mutagen 3-Chloro-4-Methyl-5-Hydroxy-2(5H)-Furanone (MCF) in Salmonella TA100 and TA104: Comparison to MX

Disinfection of drinking water by chlorination produces a number of mutagenic by-products. The chlorinated drinking water mutagen3-chloro-4-methyl-5-hydroxy-2(5H)-furanone(MCF) occurs at concentrations similar to or greater than that of the related furanone 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX). MCF and MX differ structurally only by replacement of a 4-methyl in MCF with a 4-dichloromethyl in MX; yet, MCF is significantly less mutagenic than MX and produces different adducts when reacted with nucleosides or DNA. To explore further the effects that these structural differences might have on the biological activity of MCF and MX, we determined the mutation spectra of MCF in Salmonella strains TA100 and TA104 and of MX in strain TA104. Our results show that the replacement of the 4-methyl in MCF with a 4-dichloromethyl group in MX not only dramatically shifts the mutagenic potency but also shifts the mutagenic specificity from an almost equal targeting of GC and AT sites by MCF to an almost exclusive targeting of GC sites by MX.Master of Science in Public Healt