Aim: The polymorphonuclear leukocytes (PMN) stand in the first line of the immune system and play an important role in the antitumor immunity. The reactive oxygen species derived from PMN are of crucial importance in tumor cell lysis. The aim of our work was to monitor the changes of superoxide production from PMN attributed to tumor development from the early phase to the advanced stage, and to investigate the effects of OK-432 on PMN-derived superoxide production and tumor growth. Methods: AH109a rat hepatocellular carcinoma cells were implanted into the hind leg of male Donryu rats. PMNs were harvested from rat peritoneal cavity 6 h after intraperitoneal injection of oyster glycogen. Superoxide production in response to phorbol myristate acetate (PMA) and opsonized zymosan (OZ) were measured by the method of CLA-dependent chemiluminescence, which has high sensitivity and specificity to superoxide. Results: During the experimental period, body weight and serum level of total cholesterol showed no significant difference between control rats and tumor-bearing rats. These results shows that in the experimental period tumor-bearing rats did not become cachexia. The counts of peripheral leukocytes were significantly increased during tumor progression, and there are significant difference between that of controls and tumor-bearing rats after 18 days of tumor inoculation. Both PMA and OZ-induced superoxide generation derived from PMNs became significantly reduced in the advanced stage of cancer. The suppression of PMN-derived superoxide generation was accompanied with tumor progression and an increased number of neutrophils in the peripheral blood. The subcutaneous administration of OK-432, a biological response modifier, prevented the suppression of PMN-derived superoxide generation during tumor progression, which might induce the tendency of tumor growth suppression. Conclusions: Our results suggested that the decreased superoxide generation as well as the high leukocytes concentration in the peripheral blood could be considered as indicators of an advanced stage of cancer. Furthermore, the effect of OK-432 on PMN-derived superoxide production in cancer-bearing rats may provide pharmacological evidence to the therapeutic effects of OK-432.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]