Mutagenesis, Vol. 18, No. 3, 307,
May 2003
© 2003 UK Environmental Mutagen Society/Oxford University Press
LETTER TO THE EDITOR |
Re: Chromosomal aberration, micronucleus and Comet assays on peripheral blood lymphocytes of leprosy patients undergoing multidrug treatment (Mutagenesis, 17, 309–312, 2002)
Laboratory of Carcinogenesis, Cancer Research Centre, 76 Fanardjian Street, Yerevan 52, Armenia
I studied with great interest the research findings of Kalaiselvi et al. (2002)
who evaluated the genetic damage in leprosy patients undergoing multidrug therapy (MDT) by means of the chromosomal aberrations (CA), micronuclei and Comet assays. All assays applied showed genetic damage in treated leprosy patients.
It is known that leprosy patients are different in terms of bacteriological index, immunological status, histology and clinical features (Ridley and Jopling, 1966). For genetic studies in leprosy patients, D’Souza and Das (1994) classified them into two groups, paubacillary (tuberculoid forms of leprosy) and multibacillary (lepromatous forms of leprosy). CA and sister chromatid exchange (SCE) levels, both background and induced by some mutagens, are significantly higher in multibacillary patients compared to paubacillary ones (D’Souza and Das, 1994). There is no information about the status of the patients (paubacillary or multibacillary) in the paper of Kalaiselvi et al. (2002).
As they studied possible mutagenic (genotoxic) effects of MDT, it is extremely important to mention in the text of the article the following: (i) whether the patients were primary or not; (ii) what drugs, schedules and doses were used; (iii) the duration and number of courses. These questions are extremely important for evaluation of genotoxic effects of any drug. And if any of the mentioned conditions is different for some patients, it is a serious mistake to pool the results and compare with controls.
Kalaiselvi et al. (2002) cited the paper of Masjedi et al. (2000) concerning almost the same problem, the study of genetic damage induced by MDT in tuberculosis patients. In that article, no such questions arise because of adequate presentation of materials and methods.
Kalaiselvi et al. (2002) also cited the paper of Peters et al. (1983), but they omitted the most important data presented in this paper, that patients receiving antileprosy therapy with clofazimine, dapsone and/or rifampicin do not show mutagenic/clastogenic effects. Kalaiselvi et al. (2002) wrote that ‘D’Souza et al. (1991) indicated higher incidence of CA and SCE in leprosy patients treated with MDT’. However, D’Souza et al. (1991) and D’Souza and Das (1994) actually showed that dapsone in combination with rifamoicin and dapsone with rifampicin and clofazimine did not induce CA in lymphocytes of treated leprosy patients. Moreover, in treated multibacilary patients the CA level was significantly reduced compared with the level before therapy (Peters et al., 1983; D’Souza et al., 1991; D’Souza and Das, 1994). All investigators supposed that this was due to the remedial effect of the drugs.
Hence, the three mentioned papers indicate that MDT in leprosy patients is not clastogenic, unlike the data presented by Kalaiselvi et al. (2002).
The discussion on possible mechanisms responsible for the induced genetic damage (but not cytogenetic damage, because the Comet assay is not a cytogenetic assay) in leprosy patients is not convincing. It is well documented that all studied bacterial infections [tuberculosis, brucellosis, typhus and tularemia (Ilyinskikh et al., 1986; Masjedi et al., 2000)] induce only a 2.3-fold increase in CA level in lymphocytes of patients. In leprosy patients CA level increased 2.6- and 4.2-fold compared with healthy persons (in paubacillary and multibacillary patients, respectively) (D’Souza and Das, 1994). Hence, the 9- to 12-fold increase in cytogenetic damage in leprosy patients, as presented by Kalaiselvi et al. (2002), is not due to leprosy infection itself, and assumption 1 is not true.
Assumption 2 about low blood levels of antioxidants and an excess of copper and molybdenum is unlikely because it is not possible to produce such large cytogenetic effects (Fenech, 2002) by an increase or decrease in the microelements content of blood.
The most likely explanation is assumption 3 about clastogenic effects of drugs, but these data are in contradiction of the findings of Peters et al. (1983), D’Souza et al. (1991) and D’Souza and Das (1994), although the same drugs were used in all cases.
These remarks should be taken into consideration in interpreting the otherwise interesting and important set of data presented by Kalaiselvi et al. (2002).
Notes
References
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D’Souza,D. and Das,B.C. (1994) Genotoxic effects of Mycobacterium leprae infection in humans. Mutat. Res., 305, 211–222.[Web of Science][Medline]
D’Souza,D., Das,B.C. and Thomas,I.M. (1991) Cytogenetic studies in leprosy patients before and after chemotherapy. Hum. Genet., 87, 665–670.[Web of Science][Medline]
Fenech,M. (2002) Micronutrients and genomic stability: a new paradigm for recommended dietary allowances. Food Chem. Toxicol., 40, 1113–1117.[CrossRef][Web of Science][Medline]
Ilyinskikh,N.N., Bocharov,N.F. and Ilyinskikh,I.N. (1986) Infectious Mutagenesis. Nauka, Novosibirsk, Russia.
Kalaiselvi,K., Rajaguru,P., Palanivel,M., Usharani,M.V. and Ramu,G. (2002) Chromosomal aberration, micronucleus and Comet assays on peripheral blood lymphocytes of leprosy patients undergoing multidrug treatment. Mutagenesis, 17, 309–312.
Masjedi,M.R., Heidary,A., Mohammedi,F., Velayati,A.A. and Dokohakir,P. (2000) Chromosomal aberrations and micronuclei in lymphocytes of patients before and after exposure to anti-tuberculosis drugs. Mutagenesis, 15, 489–494.
Peters,J.H., Gordon,G.R., Murray,J.E.,Jr and Simmon,V.F. (1983) Mutagenic activity of antileprotic drugs and their derivatives. Int. J. Lepr., 51, 43–53.
Rigley,D.S. and Jopling,W.H. (1966) Classification of leprosy according to immunity of five group system. Int. J. Lepr., 34, 355–373.
Received on November 14, 2002; accepted on February 3, 2003.
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