The effects of nitrogen mustard (HN2) on activities of the plasma membrane of PC6A mouse plasmacytoma cells.
Nitrogen mustard, HN2 (10(-5) M), inhibited the transport of the potassium congener 86rubidium into PC6A mouse plasmacytoma cells by 45% after a 4 hr incubation at 37 degree in vitro. HN2 (10(-3) M) had a rapid effect on the profile of 86rubidium transport into PC6A cells when added simultaneously with the 86rubidium whereas a monofunctional analogue of HN2((2-chloroethyl)dimethylamine) had no effect at 10(-3) M. The transport of the amino acid analogues alpha-aminoisobutyric acid and cycloleucine into PC6A cells was inhibited by 19% and 5% respectively after a 4 hr incubation with 10(-5) M HN2. The results suggest that the activity of plasma membrane Na+K+-ATPase may be affected by HN2. This enzyme may play a pivotal role in controlling cell growth and division. Crude cell membrane preparations from PC6A cells had variable Na+K+-ATPase activity which was possibly due to contamination with mitochondrial Mg2+-ATPase. Incubation of a crude cell membrane preparation in the presence of 40 nM dicyclohexylcarbodiimide gave constant Na+K+-ATPase activity which was inhibited by 44% on incubation with HN2 (10(-3) M) for 0.5 hr. The monofunctional analogue of HN2 inhibited this preparation by only 7% under the same conditions. It is suggested that inhibition of Na+K+-ATPase by HN2 may be an important facet of its cytotoxic activity.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D010954:Plasmacytoma / Q000188:drug therapy / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism
D000621:Aminoisobutyric Acids; D009588:Nitrogen Mustard Compounds; D000251:Adenosine Triphosphatases; D012413:Rubidium