Critical energies for SSB and DSB induction in plasmid DNA by low-energy photons: action spectra for strand-break induction in plasmid DNA irradiated in vacuum.

PURPOSE: To measure action spectra for the induction of single-strand breaks (SSB) and double-strand breaks (DSB) in plasmid DNA by low-energy photons and provide estimates for the energy dependence of strand-break formation important for track-structure simulations of DNA damage. MATERIALS AND METHODS: Plasmid pMSG-CAT was irradiated as a monolayer, under vacuum, with 7 150eV photons produced by a synchrotron source. Yields of SSB and DSB were determined by the separation of the three plasmid forms by gel electrophoresis. RESULTS: The yields of SSB per incident photon increased from 1.4x 10(-15) SSB per plasmid per photon/cm2 at 7eV to 7.5 x 10(-14) SSB per plasmid per photon/cm2 at 150 eV. Direct induction of DSB was also detected increasing from 3.4 x 10(-17) DSB per plasmid per photon/cm2 at 7eV to 4.1 x 10(-15) DSB per plasmid per photon/cm2 at 150eV. When the absorption cross-section of the DNA was considered, the quantum efficiency for break formation increased over the energy range studied. Over the entire energy range, the ratio of SSB to DSB remained constant. CONCLUSIONS: These studies provide evidence for the ability of photons as low as 7 eV to induce both SSB and DSB. The common action spectrum for both lesions suggests that they derive from the same initial photoproducts under conditions where the DNA is irradiated in vacuum and a predominantly direct effect is being observed. The spectral and dose-effect behaviour indicates that DSB are induced predominantly by single-event processes in the energy range covered.

Action spectra for single- and double-strand break induction in plasmid DNA: studies using synchrotron radiation.

Ionizing radiations deposit a wide range of energies in and around DNA and this leads to a corresponding spectrum of complexity of the lesions induced. The relationships between the amount of energy deposited and the yields and types of damage induced are important in modelling the physical and chemical stages of radiation effect and linking them to biological outcome. To study these relationships experimentally, plasmids were mounted as a monolayer and exposed in vacuum to near-monoenergetic photons from the Daresbury Synchrotron. After irradiation, the DNA was washed off and assayed for single-(ssb) and double-strand breaks (dsb) using agarose gel electrophoresis. Dose-effect relationships for ssb and dsb induction were obtained at various energies in the range 8-25 eV. The initial responses in the low-dose region allowed damage yields to be estimated. However, a common feature is that the responses showed energy-dependent plateaus at higher doses as if a fraction of the DNA were shielded. Various measures were taken both to minimize and to correct for this effect. The data appear to show that the yields of ssb and dsb increase only slowly with photon energies > 10 eV, with a suggestion of similar threshold energies for both lesions. In the energy range covered, the yield of ssb is 12-20-fold greater than that of dsb. The data indicate that ssb and dsb may have a common precursor in this system. Earlier work with low-energy electrons showed that at 25 eV ssb were induced but no dsb were detected.

Attenuation of nocturnal asthma by cromakalim.

In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.

Occupational asthma due to methyl methacrylate and cyanoacrylates.

Five patients had asthma provoked by cyanoacrylates and one by methyl methacrylate, possibly because of the development of a specific hypersensitivity response. Acrylates have wide domestic as well as industrial uses, and inhalation of vapour emitted during their use can cause asthma.

New criteria for computer interpretation of exercise electrocardiograms in a largely asymptomatic population.

We developed new discriminant functions for analyzing treadmill ECGs from a largely asymptomatic population. Treadmill ECG data were gathered from two patient groups: 70 patients with coronary artery disease with occlusions greater than or equal to 30% by angiography, and 138 patients without coronary artery disease. The group without coronary artery disease consisted of 76 false positive responders to treadmill testing using standard ST segment criteria, 22 supraventricular tachycardia patients (both groups free of coronary artery disease by angiography), and 40 patients at very low risk for having coronary artery disease. ECG leads CC5, CM5, V5, Yh and Z were recorded before, during and after exercise protocol conditions. Computer-averaged ECGs were processed to provide Q, R, S and T-wave amplitudes, ST amplitudes and slope, and QS and RT intervals. Each patient provided over 100 variables per lead for analysis. Stepwise statistical procedures yielded lead-specific linear discriminant functions containing four to six variables/lead. Application of these functions provided sensitivity and specificity in the range 70-84%. When compared with other standard interpretive criteria, these results provided improved diagnostic accuracy for the largely asymptomatic population.

Normal electrocardiographic waveform characteristics during treadmill exercise testing.

Forty asymptomatic male patients at low risk for cardiovascular disease completed maximal treadmill testing. Electrocardiograms from leads CC5, CM5, V5, Yh and Z were recorded across multiple pretest, exercise and recovery conditions. ECG waveforms were subsequently digitized, averaged and processed to provide Q-, R-, S- and T-wave amplitudes, ST-segment means and slopes, and QS- and RT-interval durations. Average R-wave amplitude increased during early exercise and then dramatically decreased to maximum effort. Average S-wave amplitude became greater as exercise progressed. Average J junction was slightly positive before exercise, became negative during exercise (except lead Z) and returned to zero after exercise. The ST-segment slope increased dramatically with progressive exercise. The response of T-wave amplitude, RT and QS intervals are also described. Separately, 22 asymptomatic male subjects each completed two maximal treadmill tests 2 weeks apart. ECG data acquisition and processing were similar to those noted above. Pooled, within-subject estimates of variability were computed for the ECG leads, ECG measurements and protocol conditions. These variability estimates are useful for interpreting ECG responses to exercise testing.