Mutational spectra of Salmonella typhimurium revertants induced by chlorohydroxyfuranones, byproducts of chlorine disinfection of drinking water
Tutkimustuotos › › vertaisarvioitu
|Julkaisu||Chemical Research in Toxicology|
|DOI - pysyväislinkit|
|Tila||Julkaistu - 1996|
The base substitution specificities of 3-chloro-4-(dichloromethyl)-5- hydroxy-2(5H)-furanone (MX), 3-chloro-4-(chloromethyl)-5-hydroxy-2(SH)- furanone (CMCF), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), and chloromalonaldehyde (CMA), a putative breakdown product of MCA, were examined in the hisG46 gene and in the hisG428 gene of Salmonella typhimurium using allele specific oligonucleotide hybridization. Although the compounds are structurally closely related, they induced substantially different mutation spectra: MCA and CMA caused primarily GC → AT transitions in the hisG46 allele (target sequence CCC), in particular, at the second position of the codon in strain TA100. In TA100 the mutation spectrum of MCA was similar to that of CMA. The mutational specificity of MCA can be explained as a consequence of misincorporation opposite to cyclic ethene adducts identical to those formed by the carcinogen vinyl chloride. The spectra induced by MX and CMCF in TA100 were almost identical but distinctively different from the spectra of MCA and CMA. Both compounds induced primarily GC → TA transversions, in particular, at the second position of the codon, and to a lesser extent in the first position of the codon. An identical site bias is induced by carcinogens such as polycyclic aromatic hydrocarbons and heterocyclic amines as a consequence of formation of (noncyclic) guanosine adducts. In hisG428 (target sequence TAA) MX induced again primarily GC → TA transversions in Tyr tRNA genes (supC/M) and, to a lesser extent, intragenic AT → TA transversions (TAA → AAA). The possible involvement of guanosine and adenosine adducts in the mutational specificity of MX is addressed.