Abstract
Antiretroviral drugs have proved useful in the clinical management of HIV-infected persons, though there are concerns about the effects of exposure to these DNA-reactive drugs. We investigated the potential of the plant model Allium cepa root tip assay to demonstrate the cytogenotoxicity of zidovudine and nevirapine and as a replace-reduce-refine programme amenable to resource–poor research settings. Cells mitotic index were determined in squashed root cells from Allium cepa bulbs exposed to zidovudine or nevirapine for 48 hr. The concentration of zidovudine and nevirapine inhibiting 50% root growth after 96 hr exposure was 65.0 µM and 92.5 µM respectively. Root length of all antiretroviral-exposed roots after 96 hr exposure was significantly shorter than the unexposed roots while additional root growth during a subsequent 48 hr recovery period in the absence of drug was not significantly different. By ANOVA, there was a significant association between percentage of cells in mitosis and zidovudine dose (p = 0.004), but not nevirapine dose (p = 0.68). Chromosomal aberrations such as sticky chromosomes, chromatin bridges, multipolar mitoses and binucleated cells were observed in root cells exposed to zidovudine and nevirapine for 48 hr. The most notable chromosomal aberration was drug-related increases in sticky chromosomes. Overall, the study showed inhibition in root length growth, changes in the mitotic index, and the induction of chromosomal aberrations in Allium bulbs treated for 96 hr or 48 hr with zidovudine and nevirapine. The study reveals generalized cytogenotoxic damage induced by exposure to zidovudine and nevirapine, and further show that the two compounds differ in their effects on mitosis and the types of chromosomal aberrations induced.
Highlights
The human immunodeficiency virus (HIV) is the retrovirus that causes the acquired immunodeficiency syndrome (AIDS)
The data indicates that ZDV is more toxic than NVP at the three highest concentrations. This observation is further supported by the EC50 values, which were calculated from the data shown in Figure 1, where 65.0 mitosise Chromosomal Fragmentsf (mM) ZDV and 92.5 mM NVP were the concentrations giving 50% inhibition of root growth length
In this study we have demonstrated the genotoxicity of ZDV and NVP for Allium root growth, for changes in mitotic index, and for chromosomal aberrations
Summary
The human immunodeficiency virus (HIV) is the retrovirus that causes the acquired immunodeficiency syndrome (AIDS). There are concerns regarding the adverse effects of ARV therapy, the perinatal exposures [1,2,3,4]. Clinical reports addressing the effects of perinatal ARV exposures in children born to HIV-positive mothers have been varied. Evidence of persistent left ventricular muscle loss was reported by Lipshultz et al, [8] to occur in some HIV-1-uninfected children born to HIV-1-infected mothers, and to be persistent for up to 2 years of age. The reversibility of these events over time has not been reported on. It is important to clarify the nature of any ARV-induced genotoxic effects, and to ascertain if these effects resolve when the drugs are withdrawn
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