Leonard L. Bennett

Studies on the mode of action of azaserine

Abstract 1. 1. Azaserine-induced inhibition of E. coli was significantly prevented by (a) 4-amino-5-imidazolecarboxamide (AIC), adenine, guanine, hypoxanthine, or xanthine; (b) methionine; and (c) glutamine; and, as has already been observed by others, by phenylalanine, tyrosine, or tryptophan. 2. 2. In studies carried out on the effect of azaserine on purine synthesis in the tumors, intestines, livers, and spleens of mice bearing Sarcoma 180, it was found that azaserine inhibited utilization of formate-C14 and glycine-1-C14 for purine synthesis, failed to affect utilization of C14-labeled adenine, AIC, and hypoxanthine, and failed to affect utilization of formate for thymine biosynthesis. Azaserine also inhibited utilization of formate-C14 and glycine-1-C14 for purine synthesis by heterologous implants of a human sarcoma growing in the rat. 3. 3. The results indicate that azaserine inhibits purine synthesis in the intact animal at a stage prior to the formation of 5-amino-4-imidazole-carboxamide ribotide.

On the metabolic stability of nucleic acids in mitotically inactive adult tissues labeled during embryonic development

Abstract [8-14C]adenine was administered to pregnant mice in order to incorporate isotope into DNA and RNA of dividing fetal tissue (brain and liver) that subsequently becomes mitotically inactive in the adult animal. The radioactivity in the DNA and RNA purines of these and other tissues from the offspring were determined at periods from nine days to one year after birth. During this period there was no loss of 14C from the DNA purines of brain and liver, whereas the RNA of these tissues did lose radioactivity. These results further confirm the metabolic stability of DNA and indicate that radioactive atoms incorporated into DNA of the liver and brain of embryos may remain fixed for the life of the animal.

Biological effects of carbon-14 incorporated into nucleic acids of mouse embryos.

The biological effects of the incorporation by the mouse embryo of high levels of C/sup 14/ were stadied in experiments in which sodium formate-C/sup 14/ or nonradioactive sodium formate was administered intraperitoneally to mice during gestation. Mice that had received formate-C/sup 14/ produced litters that were normal in all respects when compared with litters of nonradioactive animals. On the basis of the observation that C/sup 14/ incorporated during embryonic development may be retained in the DNA of certain organs for the life of the amimal, large groups of mice that had received either formate-C/sup 14/ or nonradioactive formate during embryonic development were observed over their life span in an attempt to detect radiation damage to somatic cells. As compared with nonradioactive animals, mice that had received C/sup 14/ showed no differences in weight or longevityy or in the incidence of tumors. When large groups of 2month- old males and females that had received C/sup 14/ during their embryonic development were mated with each other or with nonradioactive animals, no evidence was obtained for a lowered fertility in the groups in which the males or females or both had received C/sup 14/.