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 charact erized in our laboratory using the polycyclic aromatic hydrocarbon 3-m ethylcholanthrene (3MC). Interactions between the tumorigenic process and the natural killer cell (NK) response were investigated in this st udy. Rats given a single injection of 1.5 mg 3MC had reduced NK activi ty the first three weeks after injection when compared to vehicle trea ted controls. Tumor incidence in this group reached 45% and 76% 12 and 20 weeks, respectively, after the 3MC injection. Cell lines were esta blished 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% compare d to 32.3 to 37.5% for the NK sensitive YAC-1 target cells. Rabbit ant iasialo GM-1 antibody (ASGM-1) was used to effect in vivo reductions o f NK function at arbitrarily selected times after 3MC injection. Tumor incidence in the group of rats treated to reduce NK activity at the t ime 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 wa s also decreased from 93 to 77 days in this group. Rats treated to red uce 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 co ntrols. The study supports a role for NK cells in the early detection and removal of transformed cells and points out the dangers of transie nt immunosuppression.