This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Roosa, R. A. Articles by DeLamater, E. D. Search for Related Content PubMed PubMed Citation Articles by Roosa, R. A. Articles by DeLamater, E. D.

A Cytological Evaluation of Combined Therapy in the 6C3HED Lymphosarcoma

I. -SH-containing Analogs in Combination with Nitrogen Mustard and Mapharsen^*

Robert A. Roosa and Edward D. DeLamater

( Section on Cytology and Genetics, Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pa.)

A technic is presented for the cytologic evaluation of a tumor population of the 6C3HED lymphosarcoma after treatment with chemotherapeutic agents.

Through the use of this technic it has been possible to test, at the cellular level, the hypothesis that if one could incorporate into the chromosomes a thio-containing analog, then it might be possible to sensitize the cell to a second compound having a selective affinity for such radicals.

Thio-containing compounds, such as 6-mercaptopurine and 5-methylthiouracil, did not affect the cytologic picture when used alone, whereas 6-thioguanine and 2-thiocytosine did.

The compounds used further to test the hypothesis, nitrogen mustard and mapharsen, both produced marked cytologic abnormalities on these cells.

The cytologic data obtained showed that the combination of 6-mercaptopurine plus nitrogen mustard, 6-thioguanine plus nitrogen mustard, and 2-thiocytosine plus mapharsen supported the hypothesis by producing an effect greater than when either compound was used alone; and that the union probably occurred within the cell.

The data also show that 6-mercaptopurine and 5-methylthiouracil inactivated the effects of mapharsen, whereas it appeared that thioguanine did not combine with mapharsen, nor did 2-thiocytosine or 5-methyl thiouracil combine with nitrogen mustard.

The damage, as evidenced by the cytological studies, was, however, not paralleled by increased survival times. This paradox is discussed in the text.

^* This investigation was supported in part by a research grant PHS#C-2189 from the National Institutes of Health, Public Health Service.

This study was undertaken as a predoctoral research fellowship awarded by the National Cancer Institute, U.S. Public Health Service, and is in partial fulfillment for the degree of Doctor of Philosophy in Medical Microbiology. Present address: Wistar Institute, 36th and Spruce Streets, Philadelphia 4, Pa.

Received 4/ 4/60.