Inhibition of protein synthesis in developing mouse brain after fission neutron irradiation in utero.

Previous investigations showed that when pregnant mice were exposed to a single whole-body dose of 0.5 Gy fission neutrons on Day 17 +/- 2 of gestation [H. H. Vogel, Jr. and S. Antal, Radiat. Res. 98, 52-64 (1984)] about 40% of the newborn mice died and the body and brain weights of surviving animals decreased by 30-35%. Decreases of body and brain weights were most prominent by the third week after birth, but the content of nucleic acids related to wet weight did not change in liver and brain upon irradiation [S. Antal, A. Fónagy, Z. Fülöp, E. J. Hidvégi, and H. H. Vogel, Jr. Int. J. Radiat. Biol. 46, 425-433 (1984)]. Studies presented in this paper show that after a single whole-body dose of 0.5 Gy neutron irradiation on Day 18 of pregnancy protein synthesis decreased in liver and brain of 3-week-old mice irradiated in utero. Incorporation of labeled amino acids in vivo into acid soluble nuclear proteins decreased by 15% in liver and by 40% in brain. It was significantly reduced into brain histones and certain brain nonhistone proteins (separated by two-dimensional electrophoresis). The amount of H1 and H4 brain histones decreased as well. Investigations with isolated protein synthesizing systems proved that the peptide bond formation was not impaired by irradiation. The aminoacylation of transfer-RNA, however, decreased in both liver and brain by 26-34 and 34-41%, respectively. Comparing the aminoacylation capacities in the two unirradiated organs, a much lower (about one-third) capacity was found in brain than in liver. Moreover, this low aminoacylation capacity of brain decreased further by about 40% after neutron irradiation. These results suggest that in the developing irradiated brain the reduced capacity of aminoacylation of transfer-RNA might be rate limiting for the efficiency of protein synthesis.