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In Vivo Studies of DNA Synthesis in Human Normal and Tumor Cells^{1, 2,}

New York University Research Service, Goldwater Memorial Hospital, Welfare Island, New York, New York 10017

Studies have been made in vivo of DNA synthesis in surgically removed human tumors and in coexistent adjacent normal tissues, with the use of intravenously administered thymidine-³H as a DNA label.

The tumors investigated included two carcinomas of the colon, and one each of the rectum, stomach, oral pharynx, parotid, and ovary. The grain count has been used as an index of incorporated thymidine-³H and the interphase labeling index of cells synthesizing DNA. The DNA of the several populations was determined by two-wavelength microspectrophotometry of Feulgen-stained tissues. On the basis of the relative amounts of thymidine-³H incorporated and of the DNA contents of the respective cell populations, DNA synthesis rates and times have been deduced for coexistent normal and tumor cells.

In five of six instances where tumor and normal tissues were obtainable, the relative DNA synthesis rate was higher and the DNA synthesis time was shorter in normal cells than in tumor cells. In the sixth case it was similar. In the seventh case a relatively slow rate and time was observed but no normal tissue was available for comparison.

In three of four patients there were lower percentages of tumor cells than of normal cells, engaged in DNA synthesis. In the fourth patient the percentages were the same. The normal lymphocytes and intestinal cells were diploid and their DNA synthesis rates and times were similar. Among the six tumors for which ploidy classes were determined, three were aneuploid and polyploid and three were diploid. The growth advantages of the tumor cells in relation to adjacent normal cells do not appear to be based upon more rapid replication kinetics nor upon larger percentages of replicating cell populations. The relevance of these findings to the use of antimetabolites as chemotherapeutic agents in human tumors has been discussed.

¹ Presented in part at the 67th Annual Meeting of the American Association for Cancer Research in Denver, Colorado, May 28, 1966.

² Supported in part by the USPHS under Grants No. CA 03917-09 and HD 00672-09, in part by the Atomic Energy Commission under NYO-Contract No. 2778—Report No. 4, and by the Health Research Council of the City of New York under Contract Nos. U-1089 and U-1579.

Received 7/14/66. Accepted 12/29/66.