Tumoricidal activity, mechanism

Similar to the in vitro study using Lewis lung cells, it was observed that animals pretreated with pyran had no detectable Ehrlich ascites cells in phase GgM and only a few in the S phase after 2 or 6 days (Table XIV) (60) compared to pyran untreated mice which had 58 in the S phase and 22 in the GgM phase. Consequently, the use of pyran activated macrophage resulted in a) a high overall level of tumoricidal activity both in vivo and in vitro, b) the appearance of a tumor cell population with 50 of their normal DNA content and c) a shift of tumor cells from phase GgM to G. These results indicate that a possible mechanism of activated macrophage tumoricidal activity involves the induction of tumor cells with a reduced DNA content. 

In vivo studies illustrate a similar phenomenon (Table VII). Pyran treatment of mice resulted in a marked decrease in mitotic activity (G2M) with a concommitant shift to the resting state (cp. These results indicate that a possible mechanism of activated macrophage tumoricidal activity involves the Induction of tumor cells with a reduced DNA content. 

The uptake and location of pyran into the macrophage is of central importance in understanding the mechanism(s) by which these polyanionic polymers activate the macrophage to tumoricidal capacity. Very few studies have been addressed to this question with the exception of those performed by Pratten et al. [35]. 

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