Differential oxygen dynamics in two diverse Dunning prostate R3327 rat tumor sublines (MAT-Lu and HI) with respect to growth and respiratory challenge.

Abstract

Since hypoxia may influence tumor response to therapy and prognosis, we have compared oxygenation of tumors known to exhibit differential growth rate and tissue differentiation. Regional tumor oxygen tension was measured using 19F nuclear magnetic resonance echo planar imaging relaxometry of hexafluorobenzene, which provided dynamic maps with respect to respiratory intervention. Investigations used two Dunning prostate R3327 rat tumor sublines: the fast growing, highly metastatic MAT-Lu and the moderately well-differentiated, slower growing HI. Both sublines showed significantly higher oxygen tension in smaller tumors (<2 cm(3)) than in larger tumors (>3.5 cm(3)). Pooled data showed that MAT-Lu tumors exhibited greater hypoxia compared with the size-matched HI tumors (p < 0.0001). Respiratory challenge (oxygen or carbogen) produced significant increases in mean pO(2) for tumors of both sublines (p < 0.0001). However, initially hypoxic regions displayed very different behavior in each subline: those in the HI tumors responded rapidly with significant elevation in pO(2), while those in the MAT-Lu tumors showed little response to respiratory intervention. These results concur with hypotheses that hypoxia is related to tumor growth rate and degree of differentiation. Under baseline conditions, the differences were subtle. However, response to respiratory intervention revealed highly significant differences, which, if held valid in the clinic, could have prognostic value.