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The effects of the administration of single injections of sheep red blood cells (SRBC) and of 6-mercaptopurine (6-MP) on the synthesis of nucleic acids and proteins were studied. Under the experimental conditions, extensive antibody production was induced by the SRBC and this synthesis was blocked by the dose of 6-MP used. One day after the various treatments, inhibition of nucleic acid synthesis was seen in spleen, kidney, and liver of those animals which had received 6-MP. No extensive reduction in protein synthesis was seen. No consistent reduction was seen in the synthesis de novo of purines. Eight days after initiation of treatment, at which time antibody production was extensive, there was still a reduced incorporation of formate into DNA in the spleen of those animals which had received 6-MP or-6-MP plus SRBC. The incorporation of thymidine into DNA, on the other hand, was reduced in the spleen of animals receiving 6-MP but in those animals which had received 6-MP plus SRBC there was much less inhibition. Eight days after treatment there was still considerable inhibition of thymidine incorporation into the liver of animals which had received 6-MP alone, no change in the animals which had received SRBC, and considerable increase in those animals which had received both 6-MP and SRBC. The findings suggest a role of DNA synthesis in response to antigens. The data also demonstrate that the effects of antimetabolites persist long after they have been catabolized per se , and in view of the biological effects seen concurrently suggest general significance to these long-lived effects.

A small but persistent amount (0.1–0.6 %) of amino acids is found bound to the DNA of all tissues examined. The amount is constant and reproducible for the DNA of a given tissue taken from animals of the same species, sex and age. These observations suggest that the residues have a role. There is a difference in absolute and relative amounts of the amino acids bound to DNA from different tissues of the same species. There are also differences among the amino acids bound to the DNA of the liver of several species.