Characterization of a chemically induced tumor model and the effects of natural killer cell depletion by antiasialo GM-1.

A tumor model in the Sprague-Dawley rat has been developed and characterized in our laboratory using the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3MC). Interactions between the tumorigenic process and the natural killer cell (NK) response were investigated in this study. Rats given a single injection of 1.5 mg 3MC had reduced NK activity the first three weeks after injection when compared to vehicle treated controls. Tumor incidence in this group reached 45% and 76% 12 and 20 weeks, respectively, after the 3MC injection. Cell lines were established from six of these tumors and were tested for in vitro lysis by NK cells. Sensitivity of these cells ranged from 2.9 to 12.2% compared to 32.3 to 37.5% for the NK sensitive YAC-1 target cells. Rabbit antiasialo GM-1 antibody (ASGM-1) was used to effect in vivo reductions of NK function at arbitrarily selected times after 3MC injection. Tumor incidence in the group of rats treated to reduce NK activity at the time of initiation (0-2 weeks) reached 100% in 20 weeks compared to 67% in the companion 3MC treated controls. The number of days to tumor was also decreased from 93 to 77 days in this group. Rats treated to reduce NK activity at other times (5-7 weeks or 10-12 weeks) did not have alterations in tumor incidence or latency that were different from controls. The study supports a role for NK cells in the early detection and removal of transformed cells and points out the dangers of transient immunosuppression.