Effect of tumour growth on the macrophage response to the antitumour agent 5,6-dimethylxanthenone-4-acetic acid.

Peritoneal macrophages from C3H/HeN mice bearing subcutaneous M-16/C or Spon-2 mammary carcinomas had enhanced tumouricidal activity over control macrophages from non-tumour bearers in response to 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), a novel antitumour agent which has been scheduled for clinical evaluation. The effect of a palpable M-16/C tumour growing in C3H/HeN mice was similar to that of Bacillus Calmette-Guerin (BCG) infection, with macrophages being fully activated and tumouricidal without any further stimulus being required in culture. Macrophages from Spon-2 tumour bearing mice behaved like "primed" thioglycollate-elicited macrophages and produced a tumouricidal response to 5,6-MeXXA which was significantly higher than that obtained from resident peritoneal macrophages from non-tumour bearing mice. Resident and thioglycollate-elicited macrophages from C3H/HeJ mice were hyporesponsive not only to lipopolysaccharide (LPS), but to 5,6-MeXAA as well. Hyporesponsiveness 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, tumouricidal activity from macrophages from Spon-2-bearing C3H/HeJ mice was severely depressed compared with activity from their C3H/HeN counterparts. However, 5,6-MeXAA induced similar levels of haemorrhagic necrosis of tumours implanted in either C3H/HeJ or C3H/HeN hosts. LPS-induced haemorrhagic necrosis was significantly lower in C3H/HeJ than in C3H/HeN hosts. The results show that the presence of subcutaneous tumours modulates the activity of peritoneal macrophages in mice.