DNA Damage in Cultured L1210 Cells by 2-Haloethyl Esters of (Methylsulfonyl)methanesulfonic Acid

The effects of the 2-chloroethyl, 2-bromoethyl, and 2-fluoroethyl esters of (methylsulfonyl)methanesulfonic acid upon the DNA of cultured L1210 cells have been measured and compared with each other and with the effects of chlorozotocin. Results obtained by the alkaline elution method indicated that, at equimolar and equitoxic concentrations, the esters caused more strand scission than chlorozotocin, but at compound concentrations that caused a 50% reduction in colony formation by cells following an exposure period of 2 h, they caused no detectable crosslinking, whereas chlorozotocin did cause cross-linking. Two in vitro experimental methods that are based upon the complexing of ethidium to calf thymus DNA also yielded data showing that, at equimolar concentrations, chlorozotocin caused cross-linking of calf thymus DNA, but the 2-chloroethyl ester did not. These results indicate that these esters might not kill cells by producing DNA-DNA cross-links. The three esters caused qualitatively similar effects, but the fluoro esters caused less strand scission than the chloro and bromo esters, which caused about the same extent of strand scission.