title: DNA damage studies in untreated and treated leprosy patients.
abstract: The alkaline single cell gel electrophoresis assay was performed on peripheral blood lymphocytes of lepromatous and tubercloid leprosy patients (untreated and those undergoing treatment) in order to ascertain whether differential damage to DNA occurs. The study group included 28 male and 2 female patients and 15 healthy males who were matched for age and socio-economic status. The results revealed DNA damage in all patients, with a mean DNA migration length of 29.88 +/- 3.39 microm and 38% of their cells damaged when compared with the respective values obtained in healthy controls (1.28 +/- 0.40 microm, 5%). Multiple regression analysis for effects of confounding factors revealed antibiotic treatment in patients and alcohol consumption in controls as the only variables influencing DNA damage. In lepromatous and tubercloid patients, both untreated and those undergoing treatment, DNA damage increased significantly from that observed in control individuals, with greater increased damage in lepromatous patients. An increase in treatment time increased DNA damage linearly. Furthermore, an arbitrary classification of damaged cells (categories I-IV) was made based on observed tail lengths in leprosy patients (5.00-225.00 microm). The number of damaged cells in untreated patients was lower than in those undergoing treatment; the latter also had more cells with greater DNA migration lengths. There were no category III or IV cells in the control group. The results of the study therefore reveal that patients undergoing therapy had significantly greater DNA damage than untreated patients, indicating bacterial infection and drug therapy as the causal factors, since lepromatous-type disease is the more severe form with the patients having lower resistance to Mycobacterium leprae and requiring heavier and prolonged dosage of antibiotics. The study also corroborates that the assay offers an opportunity for correlating levels of therapy-induced DNA damage with administered dose and for modulating the dose-schedule so as to achieve lower levels of genotoxic damage.
authors.affiliation: Department of Human Genetics, Guru Nanak Dev University, Amritsar 143 005, India. jrgandhi@sancharnet.i
authors.forename: G
authors.initials: G
authors.lastname: Gandhi
authors.forename: B
authors.initials: B
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002991:Clofazimine / Q000627:therapeutic use; D004249:DNA Damage; D003622:Dapsone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007917:Leprostatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007918:Leprosy / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000627:therapeutic use
chemical_list: D007917:Leprostatic Agents; D003622:Dapsone; D002991:Clofazimine; D012293:Rifampin