Induction of abasic sites by the drinking-water mutagen MX in Salmonella TA100

• Published in: Chemico-biological interactions Vol. 180; no. 3; pp. 340 - 343
• Main Authors: King, Leon C., Hester, Susan D., Warren, Sarah H., DeMarini, David M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 14-08-2009
• Subjects: Abasic sites; Animals; Cell survival; DNA adducts; DNA Damage; Furans - pharmacology; Furans - toxicity; Mutagenicity; Mutagenicity Tests; Mutagens - pharmacology; Mutagens - toxicity; Rats; Salmonella; Salmonella - drug effects; Salmonella - genetics; Water Pollutants, Chemical - pharmacology; Water Pollutants, Chemical - toxicity; Water Supply - analysis; Mutagenicity; MX; DNA adducts; DNA damage; Abasic sites
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2009.02.016

Mutagen X (MX) is a chlorinated furanone that accounts for more of the mutagenic activity of drinking water than any other disinfection by-product. It is one of the most potent base-substitution mutagens in the
Salmonella (Ames) mutagenicity assay, producing primarily GC to TA mutations in TA100. MX does not produce stable DNA adducts in cellular or acellular DNA. However, theoretical calculations predict that it might induce abasic sites, which it does in supercoiled plasmid DNA but not in rodents. To investigate the ability of MX to induce abasic sites in cellular DNA, we used an aldehydic site assay to detect abasic sites in DNA from
Salmonella TA100 cells treated for 1.5
h with MX. At 0, 2.3, and 4.6
μM, MX induced mutant frequencies (revertants/10
6 survivors) and percent survivals of 2 (100%), 14.9 (111%), and 59.3 (45%), respectively. The frequencies of abasic sites (sites/10
5 nucleotides) for the control and two concentrations were 5.9, 6.2, and 9.7, respectively, with the frequency at the highest concentration being significant (
P
<
0.001). These results provide some evidence for the ability of MX to induce abasic sites in cellular DNA. However, the lack of a dose response makes it unclear whether this DNA damage underlies the mutagenic activity of MX.