EFFECT OF TUMOR-GROWTH ON THE MACROPHAGE RESPONSE TO THE ANTITUMOR AGENT 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID

Peritoneal macrophages from C3H/HeN mice bearing subcutaneous M-16/C o r Spon-2 mammary carcinomas had enhanced tumouricidal activity over co ntrol macrophages from non-tumour bearers in response to 5,6-dimethylx anthenone-4-acetic acid (5,6-MeXAA), a novel antitumour agent which ha s been scheduled for clinical evaluation. palpable M-16/C tumour growi ng in C3H/HeN mice was similar to that of Bacillus Calmette-Guerin (BC G) infection, with macrophages being fully activated and tumouricidal without any further stimulus being required in culture. Macrophages fr om Spon-2 tumour bearing mice behaved like ''primed'' thioglycollate-e licited macrophages and produced a tumouricidal response to 5,6-MeXXA which was significantly higher than that obtained from resident perito neal macrophages from non-tumour bearing mice. Resident and thioglycol late-elicited macrophages from C3H/HeJ mice were hyporesponsive not on ly to lipopolysaccharide (LPS), but to 5,6-MeXAA as well. Hyporesponsi veness was abrogated by BCG infection or by the presence of the M-16/C tumour, but not by the presence of the Spon-2 tumour. In response to LPS at low concentrations, or to 5, 6-MeXAA at all concentrations, tum ouricidal activity from macrophages from Spon-2-bearing C3H/HeJ mice w as severely depressed compared with activity from their C3H/HeN counte rparts. However, 5,6-MeXAA induced similar levels of haemorrhagic necr osis of tumours implanted in either C3H/HeJ or C3H/HeN hosts. LPS-indu ced haemorrhagic necrosis was significantly lower in C3H/HeJ than in C 3H/HeN hosts. The results show that the presence of subcutaneous tumou rs modulates the activity of peritoneal macrophages in mice.