Cytotoxicity and deoxyribonucleic acid damage associated with bromoacetate

Abstract

Bromoacetate, one of the hydrolysis products of bromoacetylcholine, has been shown previously to inhibit the growth of neuroblastoma cells in culture. Its mechanism of action is unknown. In this work we have further characterized the cytotoxic effect of bromoacetate in C-1300 neuroblastoma cells in culture and extended it to a cell line not of neural origin, the mouse leukemia L-1210 line. Doses required to inhibit the growth of L-1210 cells in culture were similar to those that inhibited the C-1300 line. Cytotoxicity depended on concentration and duration of exposure. L-1210 colony formation in soft agar was also inhibited by bromoacetate. Bromoacetate was shown to produce DNA single strand breaks in L-1210 cells by the alkaline elution assay. These breaks continued to form after the drug was removed from the medium. Taken together, the toxicity demonstrated toward L-1210 cells and the evidence of DNA damage following drug exposure indicate that the anti-tumor action of bromoacetate may be based on monofunctional alkylation of DNA and not related to inhibition of the cholinergic receptors.