Title: NUCLEIC ACID CHANGES AND NUCLEAR RNA POLYMERASE ACTIVITY IN EXPERIMENTAL CARDIAC HYPERTROPHY.

The Geochemical Rate/RNA Integration Study (GRIST) project sought to correlate biogeochemical flux rates with measurements of gene expression and mRNA abundance to demonstrate the application of molecular approaches to estimate the presence and magnitude of a suite of biogeochemical processes. The study was headed by Lee Kerkhoff of Rutgers University. In this component of the GRIST study, we characterized ambient nutrient concentrations and measured uptake rates for dissolved inorganic nitrogen (DIN, ammonium, nitrate and nitrite) and dissolved organic nitrogen (urea and dissolved free amino acids) during two diel studies at the Long-Term Ecosystem Observatory (LEO-15) on the New Jersey continentalmore » shelf.« less

Oligoribonucleotide binding to bakers yeast initiator tRNA was measured by equilibrium dialysis in order to determine which regions of the tRNA were free to bind complementary oligomers and which were involved in secondary and tertiary structure. Association constants of trinucleoside diphosphates and tetranucleoside triphosphates complementary to the single stranded regions of the cloverleaf structure of yeast tRNA/sub f//sup Met/ were measured at 0/sup 0/C in 1.0 M NaCl, and 0.01 M MgCl/sub 2/. The only regions of the tRNA whose complementary oligomers bound to the tRNA were the amino acid acceptor end and the five nucleotides at the 5' endmore » of the anticodon loop. These results differ from those for the other tRNAs studied by this technique; usually oligomers complementary to the dihydrouracil loop bind to the tRNA. Association constants for binding oligomers to tRNA loops were analyzed in terms of a nearest-neighbor model. Experimentally determined association free energies are then compared to predicted free energies of association and differences are attributed to tRNA tertiary structure. Two chemical models of mutagenesis are developed. They model chemical mutagenesis in bacteria and are particularly appropriate for predicting and interpreting dose response curves measured using the Salmonella mutagenesis assay developed by Ames et al.« less

The initial blockage of mitosis produced b x radiation in the rat small bowel epithelium is not accompa nied by a proportionate reduction in the rate of DNA synthesis. After very low doses of x rays there is little or no immediate effect on DNA synthesis. The drop encountered from 1 to 5 hours after higher doses is believed to be due to acute destruction of the cells involved in active synthesis. At doses of 2000 r the initial fall is much greater than 50 percent. Depending upon the dose of x rays administered DNA synthesis falls to a lowmore » level during or before the transient recovery of mitotic activity noted in the proximal postirradiation period. DNA synthesis resumes before final mitotic recovery from radiation injury begins. The length of the interval is dose- dependent. Final recovery is accompanied by an overshoot in the synthetic rate or DNA, PNA, and protein direcitly related to the time and extent of the overshoot in mitotic rate. Five hours after administration of glycine-N/sup 15/ to rats intraperitoneally the concentration of isotope in quanine of PNA and DNA in the small intestine exceeds that of adenine in both normal animals and in those dosed at various times following whole-body x radiation. After irradiation the concentration of isotope in DNA purines is reduced relatively more than in those of PNA during periods of mitotic inhibition and is increased relatively more during final recovery. Within each type of nucleic acid the purine pairs exhibit essentially parallel changes in isotope concentration. The PNA pyrimidines acquire equal isotope concentrations in normal animals, and rise in parallel fashion during periods of accelerated synthesis during recovery from x radiation. Very little if any inhibition of incorporation into PNA pyrimidines occurs at any stage after irradiation. A transient stimulation in protein synthesis occurs shortly after irradiation followed by a stimulationn of greater magnitude during the period of final recovery which is relatively smaller than the enhancement of uptake in the nucleic acids during this period. Depression below normal levels does not occur even with tissue-lethal doses which sterilize epithelial cells lining the crypts. The different classes of radiation effects observed are thought to have their origin in different classes of stem cells distinguishable by the position they occupy in the mitotic cycle. (auth)« less