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T L James

Publications and source records attributed to T L James.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effect of hypoxia on traumatic brain injury in rats: Part 2. Changes in high energy phosphate metabolism.

The effect of different degrees of hypoxia on phosphate metabolism in the brains of impact-injured rats was studied using in vivo phosphorus-31 magnetic resonance (P-31 MR) spectroscopy. Sequential changes in P-31 MR spectra within 60 minutes of insult were compared among rats with hypoxia alone, impact injury alone, or a combined impact-hypoxic insult. Hypoxia alone (PaO2 of 40 mm Hg for 30 minutes) caused no remarkable changes in phosphorus spectra except a decrease in intracellular pH. In impact-injured rats, the concentration of inorganic phosphate (Pi) increased, but signals for phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) did not change, and the ratio of PCr/Pi changed only slightly to 7% below control value. When rats with a fluid percussion impact injury of 5 atm were subjected to hypoxic conditions of a PaO2 of 40 mm Hg for 15 minutes, the PCr/Pi ratio decreased by 14%, a value significantly below that of the impact alone group (P less than 0.05). After longer periods of hypoxia (PaO2 of 40 mm Hg for 30 minutes) in impact-injured rats, there were marked increases of Pi and significant decreases in signals for PCr and beta-ATP, which caused a marked decrease in the PCr/Pi ratio to 39% below control values (P less than 0.001). Milder hypoxia (PaO2 of 50 mm Hg for 30 minutes) plus impact injury caused smaller changes in high energy metabolite concentrations, and the PCr/Pi ratio decreased to 15% below control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Binding of [1-13C]galactose-enriched hen ovalbumin to Erythrina cristagalli agglutinin as studied by 13C-NMR spectroscopy.

A study of the equilibrium binding of glycoproteins to lectins was undertaken using the titled compounds as a model system for such interactions. The binding of hen ovalbumin, enriched in galactose specifically 13C-labelled at C1, to Erythrina cristagalli agglutinin was studied by 13C-NMR spectroscopy. The lectin was shown to be bivalent for ovalbumin with an apparent estimated association constant, at infinite dilution, of about 10(4) M-1. The observed association is similar to that found for the corresponding disaccharide, Gal(beta 1-4)GlcNAc. The results strongly suggest that only the N-acetyllactosamine moiety in the carbohydrate side chain of galactose-enriched ovalbumin participates in the binding to the lectin with little, if any, interactions from other parts of either the side chain or the polypeptide backbone of ovalbumin.

Binding Sites↗
PubMed1986

Phosphorothioate-modified oligodeoxyribonucleotides. III. NMR and UV spectroscopic studies of the Rp-Rp, Sp-Sp, and Rp-Sp duplexes, [d(GGSAATTCC)]2, derived from diastereomeric O-ethyl phosphorothioates.

2D-NOE and 1H NMR chemical shift data obtained for the title oligonucleotides were compared with similar data previously reported [Broido et al. (1985) Eur. J. Biochem. 150, 117-128] for the unmodified "parent" structure, [d(GGAATTCC)]2. The spectroscopically detectable structural perturbations caused by replacement of phosphate oxygen with sulfur were mostly localized within the GsA moiety, and were greater for the Rp configuration wherein sulfur is oriented into the major groove of the B-helix. UV-derived Tm measurements gave the following order of stability for the duplexes in 0.4 M NaCl: unmodified (33.9 +/- 0.1 degrees C) approximately Sp-Sp (34.1 degrees C) greater than Rp-Rp (31.7 degrees C). The title compounds were prepared by a new and convenient synthetic route which utilized HPLC to separate the diastereomeric O-ethyl phosphorothioate precursors, (Rp)- and (Sp)-d[GG(S,Et)AATTCC], for subsequent de-ethylation by ammonia in water.

Indicators and Reagents↗
PubMed1986

Solution structure of [d(A-T)5]2 via complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect spectra and molecular mechanics calculations: evidence for a hydration tunnel.

Pure absorption phase proton two-dimensional nuclear Overhauser effect (2D NOE) spectra at 500 MHz have been obtained for [d(5'ATATATATAT3')]2 in deuterium oxide solution at several mixing times. The 100 nonexchangeable proton resonances have been assigned. The experimental 2D NOE spectra were compared with theoretical spectra calculated by using the complete relaxation matrix analysis method [Keepers, J. W., & James, T. L. (1984) J. Magn. Reson. 57, 404-426] and x-ray diffraction determined molecular coordinates of A, B, alternating B, left-handed B, C, D, and wrinkled D forms of DNA and of energy-minimized structures calculated from the most promising X-ray crystal structures by using the molecular mechanics program AMBER, in which all hydrogens, counterions, and hydration water molecules were included. The analysis of all features of the 2D NOE spectra played an important role in extracting the promising structures, and it was concluded that the wrinkled D form yields the best fit for the 2D NOE data of the A-T decamer. The molecular mechanics calculation indicated that this model structure, whose minor groove is comparatively deep and narrow, may be energetically more stable than the B form for alternating d(A-T) DNA. Interesting features of the structure include possible intra- and interchain sugar-phosphate attractions and a hydration tunnel inside the minor groove capable of accommodating three types of water molecules that aid in helix stabilization via hydrogen bonding. Counterions (sodium) serve to reduce interchain phosphate-phosphate repulsive effects.

Base Sequence↗
PubMed1986

31P NMR saturation transfer measurements of phosphorus exchange reactions in rat heart and kidney in situ.

31P NMR spectra of rat kidney and heart, in situ, were obtained at 97.2 MHz by using chronically implanted radio-frequency coils. Previous investigators have used magnetization transfer techniques to study phosphorus exchange in perfused kidney and heart. In the current experiments, saturation transfer techniques were used to measure the steady-state rate of exchange between inorganic phosphate (Pi) and the gamma-phosphate of ATP (gamma ATP) in kidney, and between phosphocreatine (PCr) and gamma ATP, catalyzed by creatine kinase, in heart. The rate constant for the exchange detected between Pi and gamma ATP in kidney, presumably catalyzed by oxidative phosphorylation, was 0.12 +/- 0.03 s-1. This corresponds to an ATP synthesis rate of 12 mumol min-1 (g wet weight)-1. Comparison of previously published O2 consumption and Na+ reabsorption rates for the intact kidney with the NMR-derived rate for ATP synthesis gave flux ratios of JATP/JO2 = 1.6-3.3 and JNa+/JATP = 4-10. The rate constants for the creatine kinase reaction, assuming a simple two-site exchange, were found to be 0.57 +/- 0.12 s-1 for the forward direction (PCr----ATP) and 0.50 +/- 0.16 s-1 for the reverse direction (ATP----PCr). The forward rate (0.78 +/- 0.18 intensity unit/s) was significantly larger (p less than 0.05) than the reverse rate (0.50 +/- 0.16 intensity unit/s). This difference between the forward and reverse rates of creatine kinase has been previously noted in the perfused heart. The difference has been attributed to participation of ATP in other reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

An in vivo 31P NMR study of cerebral hypoxic hypoxia in rats.

Twenty minutes of hypoxic hypoxia in five anesthetized rats reversibly reduced cerebral PCr and pH while ATP stayed constant. Complete metabolic and neurologic recovery occurred after oxygen was restored. Careful control of physiological parameters resulted in metabolite changes that were the same, within errors, in each animal.

Adenosine Triphosphate↗
PubMed1986

Comparison of in vivo 31P-MR spectra of the brain, liver, and kidney of adult and infant animals.

In vivo 31P-magnetic resonance spectroscopy (MRS) was used to determine the phosphorus metabolite levels in the brain and kidney of infant rabbits and adult rats and in the liver of infant rabbits and adult and infant rats. For 31P-MRS of the brain, a surface, radiofrequency coil was placed on the anterosuperior region of the head; for 31P-MRS of the liver and kidney, a radiofrequency coil was chronically implanted either between the hepatic lobes or around the kidney. 31P-MR spectra were found to show large variations in the levels of the phosphorus metabolites depending on the species, the organ, and the age of the animal. The phosphate monoester (MP)/adenosine triphosphate (ATP) ratio was significantly higher and the phosphocreatine (PCr)/ATP ratio was significantly lower in the brains of infant rabbits than in the brains of adult rats. Comparison of these data with data reported for humans and other animals suggests that these differences are due mainly to differences in age and not to differences among species. The phosphodiester (PD)/ATP ratio was found to be significantly higher in the livers of infant rabbits than in the livers of adult and infant rats - a difference more likely related to the species than to age. The kidneys of the infant rabbits showed a higher PCr/ATP radio than the kidneys of the adult rats, but this difference might be due to the influence of PCr in the surrounding muscle.

Adenosine Triphosphate↗
PubMed1986

Assessment of renal preservation by phosphorus-31 magnetic resonance spectroscopy: in vivo normothermic blood perfusion.

To evaluate the usefulness of the monophosphate/inorganic phosphate ratio (MP/Pi) in assessing renal viability in a renal transplantation setting, we monitored intracellular phosphorous metabolites of 33 canine kidneys by phosphorus-31 magnetic resonance spectroscopy (MRS) after various amounts of ischemia. Renal viability (adequate perfusion and function) was directly assessed by the presence of intraoperative urine production in each kidney. Twelve normal, well-perfused kidneys (Group 1) exhibited high control MP/Pi ratios, with a mean of 0.87 +/- 0.12. Six in situ kidneys (Group 2), subjected to 45 minutes' warm ischemia followed by reperfusion, had a mean MP/Pi ratio of 0.50 +/- 0.12 after warm ischemia, which increased by a mean of 0.50 +/- 0.11 (to 1.0 +/- 0.07) after two to four hours of reperfusion. Fifteen kidneys (Group 3) were removed, cold-flushed and transplanted after 24 hours of hypothermic storage. In eight (Group 3A), reperfusion was excellent; in seven (Group 3B), reperfusion was inadequate secondary to hypotension in two, hemorrhage in two, and renal vein thrombosis in three. Group 3A kidneys had a mean MP/Pi ratio after cold-storage ischemia of 0.54 +/- 0.08. After successful transplantation and two to four hours of reperfusion, this increased by a mean of 0.23 +/- 0.12 to 0.77 +/- 0.15. Group 3B kidneys all showed a continuous decline of MP/Pi, with a mean loss of 0.26 +/- 0.09 from baseline values (mean 0.56 +/- 0.08) to nonviable levels of 0.28 +/- 0.12 within four hours of transplantation. We conclude that MP/Pi ratios enable assessment of renal viability and ischemic damage and can predict the efficacy of renal preservation maneuvers in the dog kidney. These preliminary data support the theory that MRS can be applied to the noninvasive assessment of viability in ex vivo, cold-stored cadaveric human kidneys awaiting renal transplantation.

Animals↗
PubMed1986

Assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy.

To assess the applicability of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the analysis of renal transplant viability and preservation techniques with respect to pre-transplant ischemia, we studied two rat groups. Twenty-five rat kidneys were subjected to various time increments of warm ischemia (Group A), and 31P-MRS was performed on each kidney at time intervals of up to 72 hours during simple hypothermic storage. We correlated findings of 31P-MRS with simultaneous findings of electron microscopic (EM) ultrastructural viability parameters (in Group A) and subsequent survival and renal function in 30 rats (Group B) subjected to similar amounts of variable ischemia. Intracellular phosphorus metabolite levels were nondestructively monitored by 31P-MRS via spectral peaks of NAD, sugar monophosphates (SP), and inorganic phosphate (Pi). We concluded: SP/Pi and NAD/Pi ratios decay in a time-dependent manner for both warm and cold ischemia, although this process is much slower during cold storage; EM viability parameters correlate with the development of acute tubular necrosis (irreversible damage) versus nonviability (gross cell death) on a qualitative basis only; and 31P-MRS enables a quantitative assessment of renal viability and ischemic renal damage and can predict the degree of acute tubular necrosis and post-ischemic renal function. 31P-MRS is potentially a noninvasive, nondestructive method of assessing viability during simple hypothermic storage of the rat kidney. Preliminary evidence shows that this MRS method can be applied to human kidney viability studies for clinical renal transplantation and urologic research concerning renal preservation.

Animals↗
PubMed1986

Cerebral intracellular ADP concentrations during hypercarbia: an in vivo 31P nuclear magnetic resonance study in rats.

Qualitatively different responses of ADP levels have previously been observed in the brain during hypercarbia. One investigation has found that cerebral ADP stayed constant during hypercarbia in rats that were anesthetized with halothane, while another observed that ADP decreased during supercarbia in rats that received no supplemental anesthesia. This article reports an in vivo 31P nuclear magnetic resonance study to test the hypothesis that halothane anesthesia accounts for the discrepant observations. Isoflurane anesthesia was also studied in a second group of rats to see if a different general anesthetic agent would cause the same effects that halothane causes. The two groups of five rats underwent dual episodes of hypercarbia that were separated by a 45-min recovery period. General anesthesia, either 0.5% halothane or 1.0% isoflurane, was administered during the first episode but not during the second. Hypercarbia during halothane anesthesia caused the measured phosphocreatine (PCr) to decrease by 40%, while the calculated change in ADP was 10%, in agreement with the former investigation. In contrast, hypercarbia during either isoflurane anesthesia or no anesthesia caused a decrease of only 10% in PCr, which meant that the calculated decrease in ADP was 60%, in agreement with the results of the second investigation. We conclude that during hypercarbia, clinical concentrations of halothane, unlike clinical concentrations of isoflurane, interfere with the regulation of ATP metabolism.

Adenosine Diphosphate↗
PubMed1986

In vivo 31P-MR spectroscopy of the liver in the infant rabbit to study the effect of hypoxia on the phosphorus metabolites and intracellular pH.

In vivo 31P-magnetic resonance spectroscopy (MRS) with a chronically implanted detection coil was used to study the effect of hypoxia on the phosphorus metabolites and intracellular pH in the liver of infant rabbits. A two-turn 10-mm radiofrequency coil was placed between the hepatic lobes in each of four infant New Zealand white rabbits (10-16 days old). Two days later, the rabbits were anesthetized and mechanically ventilated with 1.5% isoflurane in 98.5% O2. Blood gases, heart rate, and mean arterial pressure were monitored. 31P-MR spectra were continuously obtained every 5 minutes during 15 minutes of hyperoxia (PaO2 greater than 250 torr), 15 minutes normoxia (PaO2 approximately equal to 100 torr), 60 minutes hypoxia (PaO2 = 24 torr +/- 4 S.D.), and 15 minutes recovery (hyperoxia). In addition, 31P-MR spectra of perchloric-acid extracts of the liver of an adult and of an infant rabbit, removed under normoxic conditions, were examined. The 31P-MR spectra of liver of the normoxic adult (in vitro) and infant rabbits (in vitro and in vivo) revealed a high level of phosphodiesters, namely glycerol-3-phosphorylethanolamine, glycerol-3-phosphorylcholine, and phosphoenolpyruvate, compared with that reported for adult rat and adult mouse liver. The inorganic phosphate (Pi)-to-adenosine triphosphate (ATP) ratio was about 0.90 during hyperoxia and during normoxia. Within 15 minutes after induction of hypoxia, the level of phosphorus metabolites changed markedly: The ATP decreased 41% +/- 18 S.D. (P less than .01) and the Pi increased 206% +/- 29 S.D. (P less than .01); the Pi/ATP ratio was 5.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Evaluation of the hereditary Syrian hamster cardiomyopathy by 31P nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy.

The relation between metabolic and functional derangement in various cardiomyopathies has not been well characterized. This information was specifically sought in a spontaneous cardiomyopathic model. Metabolic and hemodynamic parameters were obtained in glucose-perfused beating hearts of 180-200-day-old cardiomyopathic Syrian hamsters and age-matched healthy animals. This period in the cardiomyopathic hamster lifetime is intermediary between the necrotic phase and the appearance of heart failure. We used 31P nuclear magnetic resonance spectroscopy to analyze energy metabolites and intracellular pH. Cardiomyopathic hamsters had significantly higher mole fraction values for inorganic phosphate, lower phosphocreatine mole fraction as well as lower phosphocreatine/inorganic phosphate and adenosine triphosphate/inorganic phosphate ratios. Analysis of pH indicated the presence of regions of increased acidity within the heart of myopathic hamsters. Cardiomyopathic hamsters also had significantly lower left ventricular pressure, coronary flow, and myocardial oxygen consumption. Separate groups of normal and myopathic hamsters were given verapamil for 24 hours (one injection of 4 mg/kg s.c. followed by 1.2 g/l in drinking water). Verapamil-treated myopathic hamsters had evidence of markedly improved mitochondrial function when compared with untreated animals. Left ventricular pressure and coronary flow rose to normal levels. Replacing glucose by pyruvate in the perfusate of myopathic hamsters results in a marked increase in left ventricular pressure, coronary flow, and oxygen consumption with a moderate rise in phosphocreatine. Thus, 180-200-day-old cardiomyopathic hamster heart is characterized by evidence of decreased mitochondrial function, by areas of increased acidity within the heart, and by reduced left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Noninvasive spectroscopic analysis of fluoropyrimidine metabolism in cultured tumor cells.

Nuclear magnetic resonance spectroscopy is a technique that may be used noninvasively to follow the intracellular metabolism of fluorinated antimetabolites such as 5-fluorouracil (FUra) and 5-fluorouridine. Intracellular 19F spectral peaks are assigned by comparison with the pH-dependent chemical shifts measured for eight commercially available fluoropyrimidine metabolites as well as by comparison with the literature recorded values of five known catabolites of FUra. Five murine and human tumor cell lines (N1S1, Sarcoma 180, L1210, HL-60, and Mia-PaCa) were exposed in vitro for 24 h to cytostatic doses of FUra or 5-fluorouridine. Treated cells were harvested and analyzed immediately or following a subsequent incubation under either nutrient-rich or nutrient-poor conditions. A major narrow component peak at 4.6-4.9 ppm was observed in all cell samples analyzed immediately after treatment. This peak was identified as intracellular FUra nucleotides, and its T1 value was approximately 800 ms. No fluoropyrimidine catabolites were detectable in any of the treated cell lines. Free FUra could be measured in cells only after subsequent incubation under nutrient-poor conditions, and this was associated with a decline in the prominent FUra nucleotide peak. In treated cells chased with drug-free media containing 1 microM thymidine, spectra revealed a broad component signal underlying and downfield from the narrow nucleotide-containing peak. By biochemically fractionating treated cells into an acid-soluble fraction and phenol-purified cytoplasmic and nuclear RNA extracts, we were able to completely separate the nucleotide peak from the broad component signal resulting from FUra incorporation into RNA. Thymidine produced a marked enhancement of this 19F signal into both cytoplasmic and nuclear RNA without affecting the nucleotide signal from the acid-soluble fraction. The present ability of nuclear magnetic resonance to monitor the metabolic channeling of fluoropyrimidines in intact tumor cells suggests that future spectroscopic imaging of patients treated with fluorinated antimetabolites may provide clinically important information about tumor biochemistry and drug sensitivity.

Animals↗
PubMed1985

NMR studies of chromomycin A3 interaction with DNA.

The binding of chromomycin A3 to calf thymus DNA and poly(dG-dC) has been studied by 13C and 1H NMR with emphasis on the mode of binding, the role of Mg2+, and pH effects. The most prominent changes in the DNA base pair 13C NMR resonances upon complexation with chromomycin were observed for G and C bases, consistent with the G-C preference exhibited by this compound. Comparison of the 13C spectrum of DNA-bound chromomycin A3 with that of DNA-bound actinomycin D, a known intercalator, showed many similarities in the base pair resonances. This suggested the possibility that chromomycin A3 binds via an intercalative mechanism. 1H NMR studies in the imino proton, low-field region of the spectrum provided additional evidence in support of this binding mode. In the low-field spectrum of chromomycin A3 bound to calf thymus DNA, a small shoulder was observed on the upfield side of the G-C imino proton peak. Similarly, in the chromomycin A3 complex with poly(dG-dC), a well-resolved peak was found upfield from the G-C imino proton peak. These results are expected for ligands that bind by intercalation. Furthermore, in both the calf thymus and poly(dG-dC) drug complexes (in the presence of Mg2+) a broad peak was also present downfield (approximately 16 ppm from TSP) from the DNA imino protons. This was attributed to the C-9 phenolic hydroxyl proton on the chromomycin chromophore. Visible absorbance spectra at different pH values showed that the role of Mg2+ in the binding of chromomycin A3 to DNA is more than simple neutralization of the drug's anionic change.

Animals↗
PubMed1985

Two-dimensional nuclear Overhauser enhancement investigation of the solution structure and dynamics of the DNA octamer [d(GGTATACC)]2.

The resonances of nearly all 70 of the non-exchangeable protons of the duplex [d(GGTATACC)]2 in aqueous solution are assigned by proton two-dimensional nuclear Overhauser enhancement (2D NOE) spectra obtained in pure absorption phase at 500 MHz. Experimental and theoretical 2D NOE spectra are compared at each mixing time (100, 175, 250 and 400 ms) using two B-DNA structures: a standard B-form and an energy-minimized form. The GG and CC ends of the octamer duplex are well represented by the regular B-DNA structure. But large discrepancies from these models are observed for the 'TATA' box. All 2D NOE data are consistent with nanosecond correlation times, as indicated by non-selective proton spin-lattice relaxation times, but small variations in the correlation time are observed, suggesting that there are some local differences in mobility within the octamer duplex structure in solution.

Base Sequence↗
PubMed1985

Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 1. Optical and 19F NMR studies of native DNA complexes.

Lysyl-5-fluoro-L-tryptophyllysine and lysyl-5-fluoro-D-tryptophyllysine were synthesized, and their interactions with double-stranded DNA were investigated as a model for protein-nucleic acid interactions. The binding to DNA was studied by monitoring various 19F NMR parameters, the fluorescence, and the optical absorbance in thermal denaturation. The 19F resonance of the L-Trp peptide shifts upfield in the presence of DNA, and that of the D-Trp peptide shifts downfield with DNA present. The influence of ionic strength on the binding of each peptide to DNA and the fluorescence quenching titration of each with DNA indicate that electrostatic bonding (approximately 2 per peptide-DNA complex) dominates the binding in each case and accounts for the similar binding constants determined from the fluorescence quenching, i.e., 7.7 X 10(4) M-1 for the L-Trp complex and 6.2 X 10(-1) for the D-Trp complex. The 19F NMR chemical shift, line width, 19F[1H] nuclear Overhauser effect, and spin-lattice relaxation time (T1) changes all indicate that the aromatic moiety of the L-Trp complex, but not that of the D-Trp complex, is stacked between the bases of DNA. The relative increases in DNA melting temperature caused by binding of the tripeptide diastereomers are also consistent with stacking in the case of the L-Trp peptide. The magnitude of the changes and the susceptibility of the 19F NMR chemical shift to altering the solvent isotope (H2O vs. D2O) suggest that the L-Trp ring is not intercalated in the classical sense but is partially inserted between the bases of one strand of the double helix.

Animals↗
PubMed1985

Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 2. Optical, 19F NMR, and strand cleavage studies of apurinic DNA complexes.

The interactions of the diastereomers lysyl-5-fluoro-L-tryptophyllysine and lysyl-5-fluoro-D-tryptophyllysine with apurinic DNA have been examined as a model for the action of DNA repair enzymes. The binding characteristics of the tripeptide diastereomers to DNA, modified to contain approximately 5% apurinic sites, were studied by measuring 19F NMR parameters, fluorescence quenching, and activity in promoting single-strand cleavage of plasmid DNA. The affinities of each of the peptides to apurinic DNA are similar to those for native DNA. However, the 19F NMR chemical shift and relaxation behavior indicates that both diastereomers form complexes with apurinic DNA that are distinct from those formed with native DNA. In addition, the 19F NMR measurements differ for the L-Trp and D-Trp complexes with apurinic DNA. In spite of these differences, when either of the tripeptide diastereomers is incubated with plasmid DNA containing apurinic sites, no difference in the rate of single-strand cleavage of the DNA is detectable.

Animals↗