Changes in Superoxide Anion Production and Phagocytosis by Circulating Neutrophils during Tumor Progression in a Rat Model

The functional state of circulating neutrophils was monitored in a rat model of mesoblastic nephroma during tumor progression. Superoxide anion (O·2−) production in response to PMA and phagocytosis of yeast particles (Saccharomyces cerevisiae) were measured every second day after tumor cell implantation. Both phagocytosis and PMA-induced (O·2−) generation were found to be enhanced in the first period (on Days 6, 8, and 10), while they became significantly reduced in the advanced stage of cancer (on Days 12, 14, 16, and 18). The suppression of PMNL functions was accompanied with tumor progression and an increased number of neutrophils in the peripheral blood. Studies were also carried out on PMNLs isolated from normal rats and the cells were treated with plasma samples obtained from tumor-bearing animals at different stages of nephroma. Incubation of the normal cells with plasmas separated on the 2nd and 8th days of tumor growth influenced neither the (O·2−) generation nor the phagocytosis. In contrast, plasma preparations obtained on the 14th day significantly inhibited both (O·2−) production and phagocytosis by normal neutrophils. The alterations in (O·2−) generation and phagocytosis by PMNLs were observed in close association with tumor growth, thus they could be considered as indicators of tumor progression. However, further studies are required to see whether the granulocyte dysfunctions observed in our animal model could provide additional prognostic information in the case of human malignancies as well as to clarify the origin of inhibitory factor(s) present in the blood of tumorous animals.