Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism.

BACKGROUND

The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation.

METHODS

To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined.

RESULTS

Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells.

CONCLUSIONS

Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent.