High mobility group (HMG) proteins are the most abundant group of chromatin non-histone proteins. This family is composed of four major variants, including HMGB1, HMGB2, HMGB3 and HMGB4. As a highly evolutionary conserved protein, HMGB1 is the most studied and important member of this group. DAUNOMYCIN is a potent chromatin-binding antitumor drug belonging to the family of anthracycline antitumor drugs. In this work, HMGB1 was purified from rat liver and incubated with various concentrations of DAUNOMYCIN and then its binding to DAUNOMYCIN was investigated, using equilibrium dialysis and circular dichroism spectroscopy techniques. The Scatchard plot obtained from the equilibrium dialysis study exhibited positive cooperative binding behavior and the occurrence of a negative Gibbs free energy (DGo = -6.57 Kcal/M), suggesting that the interaction process was exergonic. Association (Ka) and dissociation (Kd) constants were also determined (Ka: 7.71 ´ 104 M-1, Kd: 1.3 ´ 105 M). According to the circular dichroism data, upon addition of various concentrations of the drug, secondary structure of HMGB1 was altered in a dose dependent manner. Prediction of secondary structure of HMGB1 using relevant software showed that upon binding of DAUNOMYCIN to HMGB1 the alpha-helical content of the protein was increased. Summing up, the results suggest that DAUNOMYCIN binds to HMGB1 protein and this binding may influence HMGB1-DNA interaction followed by DNA-dependent activities of the protein in the cell.

In this study the interaction of antitumor antibiotic, DAUNOMYCIN with histone H1 in different ionic strengths was investigated employing UV/Vis and fluorescence spectroscopy. The results show that binding of DAUNOMYCIN to histone H1 reduces protein absorbance at 210 nm and the amount of denatured protein is dependent on drug concentration. By increasing drug concentration, binding constant is increased whereas denatured free energy is decreased. Increasing the ionic strength intensifies the effect. Fluorescence spectroscopy also shows that the interaction of DAUNOMYCIN with histone H1 reduces the intensity of the fluorescence at tyrosine position and produces hypochromicity. The results suggest that DAUNOMYCIN binds to histone H1 and quenches tyrosine residue in the protein. In the chromatin, histone H1 can also be considered as a target for antitumor anticancer drugs.  

Background: This study was done to determine the frequency of cardiomyopathy related to DAUNOMYCIN in children and adolescents with improved acute lymphoblastic leukemia and its relationship with cardiac troponin-T and cumulative dose of drug.Methods: This cross sectional study was conducted on children and adolescents under age 18 years with improved acute lymphocytic leukemia disease (ALL) and a history of receiving DAUNOMYCIN who referred to Al-zahra hospital, Iran. People with inclusion criteria based on cumulative dose of DAUNOMYCIN were divided into two groups. First group of patients were those who received cumulative DAUNOMYCIN dose fewer than 250 mg/m2 and second group with cumulative dose equal to or greater than 250 mg/m2. In all patients after obtaining consent and taking history, blood levels of cardiac-troponin-T and Shortening Fraction (FS) and Ejection Fraction (EF) indices was measured. Collected data was analyzed by SPSS.Findings: Among 55 patients treated with DAUNOMYCIN, three patients were diagnosed with cardiomyopathy, all of which were in the second group (P<0.048). The mean EF in the first group and second group were respectively 65.03+4.26 and 61.4+6.56 (P<0.02). The mean SF in the first and second group were respectively 34.23+4.19 and 31.92+4 (P<0.04). Cardiac troponin-T test result was positive in 4 patients from the second group but in the first group there were no positive tests (P<0.037). There was no significant relationship between cardiomyopathy and increased level of cardiac troponin-T (P=0.21).Conclusion: Acute lymphocytic leukemia patients treated with DAUNOMYCIN were at risk for cardiac complications. It is recommended to avoid therapy with a dose more than 250 mg/m2. Since there was not any correlation between cardiac troponin-T level and cardiomyopathy, cardiac troponin-T can not be a reliable marker of delayed cardiotoxicity.

Purpose: To compare the success rate of adjunctive 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH), and DAUNOMYCIN in combination with triamcinolone during vitrectomy in eyes with retinal detachment (RD) and proliferative vitreoretinopathy (PVR).Methods: In this prospective randomized clinical trial, 69 eyes from 69 patients with RD and PVR (grade B or C) randomized to 3 groups. Group 1: received 5-FU and LMWH (200 microgram/ml 5-FU and 5 IU/ml LMWH, Fragmin); group 2: received DAUNOMYCIN (0.5 mg) in 500 cc infusion fluid; and group 3: control group. In all patients, 0.1 cc intravitreal triamcinolone was used during vitrectomy. The patients visited on day 1, week 1, month 1, 3 and 6. Best corrected visual acuity (BCVA) and retinal status compared in the 3 groups.Results: Complete data were available for 60 out of 69 patients. Thirty five patients (58.3%) were male and 25 patients (41.7%) were female. The patient age range was 19-84 years and the mean age was 49. The groups did not have significant difference in age, sex, duration of detachment, severity of PVR, preoperative visual acuity (V/A), lens status, type of tamponade and encircling band and buckle. Postoperative V/A and retina status also was the same in the 3 groups.Conclusion: Perioperative infusion of 5-FU, LMWH and DAUNOMYCIN does not significantly increase the success rate of patients with RD and PVR comparing to control group. Although visual acuity improvement and retina reattachment rate in group 1 and 2 were better than control group, but statistical analysis failed to show significant difference between the 3 groups.