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1. Phagocytic activity measured by means of the intravasal clearance of a soot dispersion in male NMRI-mice was increased six to ten days after whole-body X-irradiation (640 R) and decreased during the same period after i.v. administration of 2,4,6-triethyleneimino-s-triazine (TEM 2.0 mg/kg). 2. By means of 6-methyl-uracil food admixtures (200 to 400 ppm during 2 or 3 weeks) or by repeated intravenous injections of a N-methyl-D-glucosamine-6-methyluracil complex (62.5 to 250 mg/kg daily during five days), a significant augmentation of the phagocytic index being related to time and dosage was obtained in otherwise untreated mice. Comparable results were seen using cytidine and cytidine-s'-phosphate, whereas guanosine-5'-phosphate remained ineffective. 3. Whilst stimulating effects of 6-methyl-uracil or its N-methyl-D-glucosamine complex on X-irradiated mice were suspended, an increase up to supernormal values of the phagocytic index was produced by the pyrimidine base in animals treated with TEM. In accordance to this the survival rate of lethally X-irradiated mice (960 R) could not be increased; with animals given lethal TEM-doses, however, a significantly increased survival rate was obtained. 4. The present investigations as well as former biochemical analyses confirm the assumption that 6-methyluracil produces its regeneration effects, to some extent at least, by specific pathways influencing the reticuloendothelium. Different results from X-irradiated and TEM-treated mice are referring to the different points of attack of the two noxa.

The in vitro incorporation of 14C-thymidine into DNA of bone-marrow cells as well as DNA content of spleen and thymus of male Wistar rats were increased significantly by 6-methyluracil (within an N-methyl-D-glucosamine-6-methyluracil complex) and/or heterologous, low-molecular nucleic acids, when given therapeutically at doses of 100--250 mg/kg b.w. following i.v. injection of tretamine. Maximum effects were reached as early as two days after the onset of experiment. When tretamine was replaced by X-irradiation or cyclophosphamide, the influence of the 6-methyluracil complex and nucleic acids was less significant. Whereas normal bone-marrow cells and cells damaged in vitro by X-irradiation, tretamine and/or inhibitors of protein synthesis could not be influenced by the 6-methyluracil complex, incorporation of 14C-L-phenylalanine into proteins of bone-marrow cells was enhanced by exogenous DNA or RNA (10--100 micrograms/ml). The present investigations underline the previously drawn conclusions that certain biological alkylating agents, nucleic acids and pyrimidines may interfere to some extent through the reticuloendothelial system.

Survival time of mice after i.v. injections of 2,4.6-triethylene-imino-1,3,5-trazine (TEM) or total body-X-irradiation (TBI) was increased by 6-methyluraclil (6-MU) when given in food (200 ppm). Under the same conditions, 6-MU decreased the involution of spleen and thymus (as measured by DNA-content and DNase II activity) under the infuence of TEM and enhanced the regeneration of the spleen after TBI. Elevation of DNase I- and protein content of the kidneys and a (short-dated) increase of incorporation of 14C-phenylalamine into microsomes of liver of 14C-orotic acid into RNA of liver and kidney suggest that the influence of 6-MU is mediated at least partly by a specfically anabolic effect.