Micronuclei induced by reverse transcriptase inhibitors in mononucleated and binucleated cells as assessed by the cytokinesis-block micronucleus assay

Lourenço, Eloir D.; Amaral, Viviane Souza do; Lehmann, Maurı́cio; Dihl, Rafael Rodrigues; Schmitt, Virgínia M.; Cunha, Kênya Silva; Reguly, Maria Luı́za; Andrade, Heloı́sa Helena Rodrigues de

doi:10.1590/s1415-47572010005000084

Cited by 6 publications

(6 citation statements)

References 24 publications

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“…The different results between both studies could suggest that not only AZT but the combination of HIV infection and AZT lead to increased chromosomal damage. The in vitro genotoxicity effects of AZT and 3TC seen in studies of Stern et al [29], Lourenco et al [28], and Gonzalez Cid et al [30] were not confirmed in the current study. The fact that in these studies, ART was added in high concentrations for short terms in vitro to cell cultures, while in this study the ART was administered in vivo over a longer period, could explain the observed difference.…”

Section: Discussioncontrasting

confidence: 86%

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The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

Herd¹,

Francies²,

Slabbert³

et al. 2014

J AIDS Clin Res

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Introduction: Antiretroviral Treatment (ART) has led to an improvement in survival of HIV infected individuals. Some of them will develop cancer during the course of their infection and will require radiation therapy. HIV positive cancer patients have presented with adverse side effects of radiotherapy and elevated chromosomal radiosensitivity. This study investigated if ART has an influence on chromosomal radiosensitivity of HIV positive individuals. Methods and Materials:Blood samples from 60 HIV positive individuals were in vitro exposed to doses of X-rays of 0, 2 and 4Gy and chromosomal radiosensitivity was assessed with the micronucleus assay. The micronucleus assay was also performed on lymphocytes of a group of non HIV-infected health care workers taking prophylactic post-exposure ART to measure the effect of these ART drugs on chromosomal radiosensitivity without HIV as a confounding factor.Results: All HIV patients (those on ART and without ART) had significantly higher radiation induced Micronuclei (MN) than healthy controls. The MN yields increased in the HIV patients taking ART compared to HIV patients not on treatment. The evaluation of chromosomal radiosensitivity of health care workers on ART revealed no effects of ART. Conclusions:HIV positive individuals show an increased chromosomal radiosensitivity. Antiretroviral treatment given to HIV positive individuals can lead to enhanced chromosomal radiosensitivity and therefore impose higher risks for radiotherapy side effects in these patients.

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Section: Discussioncontrasting

confidence: 86%

“…The micronucleus assay is also considered a sensitive method to evaluate the cytotoxic potential of an active agent. The nucleoside reverse transcriptase inhibitors AZT, 3TC and d4T have been shown to produce an increase in MN in human lymphocyte cultures [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

Herd¹,

Francies²,

Slabbert³

et al. 2014

J AIDS Clin Res

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“…However, AZT and 3TC individually tested showed induction of micronuclei in cultured human lymphocytes in binucleated cells using the cytokinesis-block micronucleus (CBMN) assay [13,14]. In the present study, TDF + 3TC exhibited clastogenic and/or aneugenic effects on MNPCE induction.…”

Section: Discussionmentioning

confidence: 54%

Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow

et al. 2016

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Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.

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“…Only few studies have tried to explain the MN formation. Shimura M et al and Tachiwana H et al have linked this process to the action of the accessory gene Vpr of HIV, which induces double-strand breaks of chromosomal DNA [21, 22], while Lourenco ED and colleagues justify it with a clastogenic (chromosome breakage) and aneugenic (chromosome loss) action of the therapy [39]. …”

Section: Discussionmentioning

confidence: 99%