The effect of 3-methylcholanthrene on mouse natural killer cells in vitro.

The effect of the chemical carcinogen 3-methylcholanthrene (3-MCA) on mouse natural killer (NK) cells was tested in vitro applying kinetic analysis of the NK-tumor cell interaction. 3-MCA inhibited the lytic activity of spleen cells against YAC-1 target cells in a dose-dependent manner. Maximal inhibition, of Vmax was about 60% and a parallell decrease in KM values was observed. Inhibition was observed after 30 min preincubation of effector cells while pre-incubation of target cells had no effect. Inclusion of Indomethacin in the assay to exclude the possibility that prostaglandins induced by 3-MCA were the mediators of NK suppression had no effect. 3-MCA inhibited basal and interferon-activated NK lysis to about the same extent, while Vmax and KM values of effector cells pretreated with 3-MCA and assayed in the presence of interferon was close to control values. In a single cell assay for NK activity it was found that 3-MCA interfered with the lytic step of NK mediated lysis without affecting target binding. These data are in accordance with an earlier observation that a single injection of 3-MCA transiently inhibited mouse NK cells in vivo and evidence is presented that 3-MCA inhibits the lytic activity of a subpopulation of NK cells. The effects of 3-MCA were reversed by interferon.