Studies on Chemical Protection against Radiation. I. the Protective Effect of Orotic Acid against X-radiation Death in Mice.

An experiment was carried out to determine the protective effect of orotic acid (uracil-4-carboxylic acid) against X-rays. Orotic acid in dose of 0.05, 0.1, 1.0, 1.7 and 10 mg per mouse was given intra peritoneally to mice before or after a single dose whole-body X irradiation of 700 r or 550 r, after which the 30-day survival rate was observed. As a result it was concluded that it would be difficult to state that orotic acid has a protective effect against X-irradiation. It may be added that even if a protective effect exists it would be slight. Recently, studies on chemical protection against radiation damage have become a matter of interest. Orotic acid (uracil-4-carboxylic acid) was discovered in milk in Italy by Bis caro3). Makinol.2>, Novak and Hauge5) confirmed that orotic acid is a precursor of nucleotides and has a growth stimulating effect, and that it reduces the occurrence of chronic liver damage induced by thioacetic amid and heliotropin. Further, many authors have recognized its effectiveness on liver lesion. Thus, orotic acid is being widely used clinically. The present animal experiment was conducted on the protective effect of orotic acid against lethal doses of X-ray. MATERIALS AND METHODS Male mice of DM/MK strain weighing approximately 20 g were used. The physical factors of irradiation were: 200 kVp, 25 mA, filter 0.3 mm Cu+0.5 mm Al, HVL 0.9 mm Cu, focus-animal distance 44 cm, and dose rate 120 r/min. Single whole-body X-irradiations of 700 r or 550 r were given to animals and the 30-day survival rate was observed. Fig. 1. The 700 r groups administered with orotic acid one hour be fore irradiation. Fig. 2. The 700 r groups administered with orotic acid 10 min. be fore irradiation. Fig. 3. The 700 r groups administered with orotic acid immediately after irradiation. Fig. 4. The 700 r groups administered with orotic acid every day for 10 days after irradiation. Fig. 5. The 700 r groups administered with orotic acid every day from immediately after irra diation to death. Orotic acid was given intraperitoneally to mice in the doses and at the times stated below. Mice were divided into three groups. The first group was admini stered 700 r of single whole-body X-irradiation, the second was given 550 r, and the third was not irradiated. The 700 r group was subdivided as follows: Subgroup 1. Orotic acid in doses of 1.7 or 10 mg per mouse was given one hour before irradiation. Each group was composed of 10 mice. Subgroup 2. Orotic acid in doses of 0.1, 1.0 and 10 mg per mouse was given 10 minutes before irradiation. Each group consisted of 5 mice. Subgroup 3. Orotic acid in doses of 0.1, 1.0 and 10 mg per mouse was given im mediately after the irradiation. Each group consisted of 5 mice. Subgroup 4. Orotic acid in doses of 0.1, 1.0 and 10 mg per mouse was given every day to mice for 10 days from immediately after irradiation. Each group con sisted of 5 mice. Subgroup 5. Orotic acid in doses of 0.1 and 0.05 mg per mouse was given every day to mice from immediately after irradiation to death. Each group consisted of 10 mice. Subgroup 6. X-irradiation with 700r only. 5 mice. In the 550r group, the doses of orotic acid per mouse were as follows: 1), 2) 0.1 and 0.05 mg 10 minutes before irradiation. 3), 4) 0.1 and 0.05 mg every day from immediately after the irradiation to death. 5) Irradiation with 550r. No injections. In the third, non-irradiated group : mice were given orotic acid in dose of 1.0 or 10 mg per mouse for 10 days, and weighed every day for 30 days. Table 1. 30-day survival of mice exposed to whole-body X-irradiation with 550 r RESULTS The results of the 700 r subgroups are illustrated in Figs. 1-5. No animals survived for 30 days. Regardless of time of injection, a slight prolongation of life was observed in the groups receiving less than 1.0 mg of orotic acid per mouse. The results of the groups administered 10 mg of orotic acid per mouse seems to be worse than of the control. Thus, it may be said that in the 700 r subgroups the protective effect of orotic acid against X-irradiation was not significant, even if it did exist. As a slight protective effect seemed to be present in the groups receiving less than 1.0 mg of orotic acid, and it was surmised that if the dosage of irradiation were reduced the protective effect of orotic acid might become apparent, thus, an experiment with 550r was performed. The results of the 550r subgroups are summarized in Table 1. A statistical analysis of these results by Chi-square test indicates that the differences between any group and control one are insignificant (p=0.05). Thus, it would be difficult to state that orotic acid has a protective effect against X-irradiation. Even if a protective effect exist, it would be slight. Although Makinol> reported that orotic acid had a growth stimulating effect, in the present experiment loss in weight of animals was observed in the 10 mg group of the non-irradiated animals and 3 out of 5 mice died on the 10th day after the beginning of injections.