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.

Animals↗

PubMed1978

Unscheduled DNA-synthesis in UV-irradiated spleen lymphocytes of the rat after whole-body X-irradiation.

Unscheduled DNA-synthesis of UV-irradiated spleen lymphocytes of the rat is inhibited in a dose-dependent manner by total-body X-irradiation. The reaction is observed immediately after exposure and reaches its maximum within 8--16 h. Doses of some rads are detectable. Following sublethal X-irradiation (250 rad), regeneration takes 4--6 weeks. Analogous results have been obtained in rats treated with 2,4,6-triethyleneimino-1,3,5-triazine. Regardless of the action mechanisms, it is concluded from the present results that the inhibition of the unscheduled incorporation of thymidine-3H in splenic lymphocytes is a very sensitive, though not specific expression of impairment of the lymphatic system.

Animals↗

PubMed1977

E1On the effect of 6-methyluracil on mice damaged by 2,4,6-triethylene-imino-1,3,5-triazine or by X-irradiation (author's transl).

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.

Animals↗

PubMed1977

[Influence of whole-body X-ray irradiation and 2, 4, 6-triethyleneimino- 1, 3, 5-triazine on the hypnotic effect of hexobarbital in mice (author's transl)].

The hypnotic effect of hexobarbital, measured in male NMRI-mice, was reduced during the first 24 hours after a unique or fractionated whole-body X-ray irradiation with 700 and 1400 R resp. 70 to 280 R and twelve hours after a unique intravenous injection of 16,0 mg tretamine per kilogram of body weight. Immediately after a unique injection of a high dose of tretamine and 24 hours after the last of four applications of 0,25 to 2,0 mg/kg which were repeated each after one day, the sleeping time after hexobarbital was prolonged. 24 hours after fractionated injection of tretamine (0,5 mg/kg each time), the concentration of hexobarbital in the brain showed a significant increase compared with the control animals. These results show that the decreased effect of hexobarbital in the early post-irradiation phase is based on pharmacodynamic processes while the increase of the effect produced by continued administration of tretamine can be explained by pharmaco-cinetic reasons.

Animals↗

PubMed1975