The ability to repair damage to DNA was compared in 2 groups of patients having undergone treatment for leukemia, one of which developed secondary leukemia (SL), and the other without signs of secondary malignancy (treated controls). Both were related to normal controls. DNA repair was assessed in isolated peripheral lymphocytes from the patients by measuring the rejoining of strand breaks following alkylation damage to the lymphocytes or by measuring unscheduled DNA synthesis. Day-to-day variability in the assays was considerable, but findings were that 5 out of 7 SL patients had repair deficiencies as measured by their ability to rejoin strand breaks, and 5 out of 7 had increased unscheduled DNA synthesis compared to treated and normal controls. All patients with SL and 4 out of 8 treated controls had inherent strand breaks in their DNA as compared to the normal controls when measured by alkaline elution.

Adult↗

PubMed1985

Repair of 8-methoxypsoralen induced DNA interstrand cross-links in Tetrahymena thermophila. The effect of inhibitors of macromolecular synthesis.

The effect of several growth-inhibiting compounds on the repair of 8-methoxypsoralen-UVA-light-induced DNA interstrand cross-links has been studied in the protozoan Tetrahymena thermophila. The repair process was analyzed by the alkaline elution technique and could be divided into 3 phases: a protein-DNA complexing phase, a DNA-incision phase and finally a DNA-ligation phase. The incision was found to be completely inhibited by novobiocin (50 micrograms/ml), nalidixic acid (150 micrograms/ml), n-butyrate (15 mM) and cycloheximide (1 microgram/ml), while no effect was observed for cytosine-1-beta-D-arabinofuranoside (10 mM), puromycin (1 mM), hydroxyurea (5 mM) or 3-aminobenzamide (2.5 mM). None of the compounds showed any effect on the protein-DNA complexing step, and the ligation was partly inhibited only by nalidixic acid (150 micrograms/ml). The involvement of topoisomerases in the repair of psoralen-induced DNA interstrand cross-links is suggested.

DNA Repair↗

PubMed1982

The effect of aphidicolin in DNA repair on resting and mitogen stimulated human lymphocytes.

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Aphidicolin↗

PubMedDate not supplied

Dofetilide in patients with congestive heart failure and left ventricular dysfunction: safety aspects and effect on atrial fibrillation. The Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group.

INTRODUCTION. Atrial fibrillation is a frequent cause of worsening of symptoms in patients with congestive heart failure. The drugs currently available for maintenance of sinus rhythm all have major side effects. METHODS. In 34 Danish coronary care units, 1518 patients with congestive heart failure and reduced left ventricular systolic function were randomized to receive either placebo or a new class III antiarrhythmic drug, dofetilide. The dose of dofetilide was adjusted according to the presence of atrial fibrillation, the length of the QT interval, and renal function. Patients were continuously monitored electrocardiographically for the first 3 days of the study. The primary end point was all-cause mortality and follow-up was for at least 1 year. RESULTS. In the dofetilide/placebo groups, 311/317 patients died (41%/42%). The hazard ratio for dofetilide treatment was 0.95 (95% confidence interval, 0.81-1.11). Treatment with dofetilide reduced worsening of heart failure significantly (hazard ratio, 0.75; 0.63-0.89). After 1 year, 61% of patients with atrial fibrillation at the start of the study had converted to sinus rhythm on dofetilide, vs. 33% in the placebo group. After conversion to sinus rhythm, 78%/43% of patients in the dofetilide/placebo groups remained in sinus rhythm for at least 1 year. There were 25 instances (3%) of torsade de pointes ventricular tachycardia in the dofetilide group and none in the placebo group. CONCLUSION. In patients with congestive heart failure, dofetilide can effectively convert atrial fibrillation to sinus rhythm and maintain sinus rhythm after conversion. Hospitalization for congestive heart failure is reduced. Dofetilide does not affect mortality. (c)2001 by CHF, Inc.

Journal Article↗