Assessment of complex genomic alterations induced by AZT, 3TC, and the combination AZT +3TC.

Allyne Cristina Grando, Nilza Nascimento Guimarães, Ana Paula de Souza, Mauricio Lehmann, Kênya Silva Cunha, Rafael Rodrigues Dihl

Drug and chemical toxicology 2020 Jul

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Highly active antiretroviral therapy (HAART) regimens are based on the use of nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs used by patients infected with the human immunodeficiency virus (HIV). The use of NRTIs combinations has afforded clear clinical benefits to patients undergoing HAART. However, the combination of two NRTIs may increase the risk of genomic instability in comparison with the drugs administered individually. We analyzed the ability of zidovudine (AZT) and lamivudine (3TC), and the combination AZT +3TC to induce complex genomic alterations using the cytokinesis-block micronucleus (CBMN) assay in Chinese hamster ovary (CHO)-K1 cells. The 24-h cell treatment with individual NRTIs showed that AZT increased micronucleus frequencies and nucleoplasmic bridges (NPBs). No significant differences were observed for any parameters investigated after exposure of CHO-K1 cells to 3TC. The combination AZT +3TC significantly increased micronucleus frequencies. Analysis of interaction between these drugs suggested that antagonism occurs in all AZT +3TC concentrations. These results highlight the importance to investigate the genotoxic profile of NRTIs to develop safer intervention strategies in antiretroviral treatment protocols.

Citation

Allyne Cristina Grando, Nilza Nascimento Guimarães, Ana Paula de Souza, Mauricio Lehmann, Kênya Silva Cunha, Rafael Rodrigues Dihl. Assessment of complex genomic alterations induced by AZT, 3TC, and the combination AZT +3TC. Drug and chemical toxicology. 2020 Jul;43(4):429-434