Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow.
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.
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Aroldo Vieira de
AV
Moraes Filho
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Cláudia de Jesus Silva
CJ
Carvalho
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Cristiene Costa
CC
Carneiro
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Camila Regina do
CR
Vale
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Débora Cristina da Silva
DC
Lima
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Wanessa Fernandes
WF
Carvalho
Programa de Pós-Graduação em Ecologia e Conservação, Universidade do Estado de Mato Grosso, Campus Universitário de Nova Xavantina, BR 158, Caixa Postal 8, 78.690-000, Nova Xavantina, MT, Brazil.
Thiago Bernardi
TB
Vieira
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Daniela de Melo E
DM
Silva
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Kênya Silva
KS
Cunha
Laboratório de Radiobiologia e Mutagênese, Departamento de Genética, Instituto de Ciências Biológicas (ICB), Campus Samambaia, Universidade Federal de Goiás (UFG), Caixa Postal 131, 74001-970, Goiânia, GO, Brazil.
Lee
L
Chen-Chen
D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D001853:Bone Marrow / Q000187:drug effects; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D000068698:Tenofovir / Q000008:administration & dosage* / Q000009:adverse effects; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D004338:Drug Combinations; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir