Regional thymidine transport and incorporation in experimental brain and subcutaneous tumors

The regional distribution and local incorporation of [14C]thymidine into a nonextractable tissue fraction, probably DNA, was measured in normal and neoplastic tissues. We studied brain tumors induced by avian sarcoma virus and ethylnitrosourea, and transplanted RG-2 intracerebral and subcutaneous gliomas. An incorporation quotient, Q, was calculated for different tumor regions and brain from the methanol nonextractable radioactivity in the tissue and the plasma concentration-time integral of thymidine. The incorporation quotient represents the rate of clearance of thymidine from blood and its incorporation into macromolecules (probably DNA). The values of Q were compared with a labeling index measured in the same tissue regions with conventional autoradiography. The following observations were made: (1) the mean plasma half-life of thymidine was 6.5 min; (2) the regional incorporation quotient in tumors varied from values comparable to normal brain to more than 100 times higher; (3) RG-2 tumors had significantly higher Qs than the other tumor models; (4) Q in subcutaneous tumors varied most widely (greater than 500-fold range); (5) the labeling index reflected the values of Q in some tumor regions but not in others; differences between the two were most frequently related to tumor cell density and the intensity of individual tumor cell labeling. A comparison of these data with previous studies of capillary permeability and blood flow in these tumor models indicates that the incorporation of [14C]thymidine into a nonextractable tissue fraction can be limited by transcapillary transport in brain tumors and by blood flow in systemic tumors, and that thymidine disposition in these tumors is not always indicative of the rate of DNA synthesis.