Azidothymidine (AZT) as a Potential Modifier of Radiation Response in Vitro

Abstract

The potential effect of AZT as a thymidine analogue on radiation response in vitro was investigated. Two human cell lines (WiDr and HeLa) were used. The effect of 10 microM AZT on exponentially growing cells was studied after different exposure times (24, 48 and 72 h). The surviving fraction (clonogenic assay) or metabolic activity (MTT assay) after irradiation of AZT-exposed cells, was compared to unexposed irradiated controls. Flow cytometry was used to assess the cell-cycle effect of pre-exposure of exponentially growing cells to AZT. AZT had a radioprotective effect for all experimental time points as far as WiDr was concerned. For HeLa the effect was significant at 24 h. Cell-cycle analysis showed a significant accumulation in S-phase at 72 h for WiDr. For HeLa there was a significant accumulation in S-phase at 48 h. We conclude that under the reported experimental conditions, AZT as a thymidine analogue seems to reduce the cytotoxic effect of irradiation.

The Effect of HIV and Antiretroviral Therapy on Chromosomal Radiosensitivity

“…Jagetia and Aruna [25], found that administration of AZT to Hela cells before exposure to different doses of γ-radiation resulted in a significant elevation in the yield of MN. This was in contrast to Copaceanu et al [26] who suggested radioprotection of AZT in Hela cell lines exposed to irradiation in-vitro. Several publications demonstrated that AZT and 3TC alter cell cycle kinetics and increase the proportion of cells in S phase [21,22].…”

“…Radiosensitivity of cells differs according to cell type and phase of the cell cycle the cells are in at the time of irradiation [37]. In both studies of Jagetia and Aruna [25] and Copaceanu et al [26] irradiations were performed on rapidly-dividing Hela cell lines, while in the current study, lymphocytes were irradiated in the G0 phase of the cell cycle.…”

“…Since NRTIs interact with host DNA, inhibit mammalian DNA polymerases and affect the cell cycle [21], it is possible that they have an impact on DNA damage repair and affect chromosomal radiosensitivity. Some studies have shown antiretroviral drugs to be radioprotective while others have suggested a radiosensitising effect [25,26]. For the first part of this study we investigated the chromosomal radiosensitivity of HIV patients not on ART, HIV patients on two common ART regimens (d4T+3TC+EFV and TDF+3TC+EFV) and compared it to healthy uninfected controls.…”

“…AZT, 3TC and TDF have been shown to inhibit cell growth [20], to interfere with cell cycle arrest, induce cell death by apoptosis and inhibit telomerase activity [21][22][23][24]. Conflicting studies have shown AZT to act as a radioprotector or a radiosensitizer [25,26].…”

Doses and Time‐Dependent Effects of 3′‐Azido‐3′‐deoxythymidine on T47D Human Breast Cancer Cells in vitro

“…Our results show that azidothymidine, at concentrations ranging from 3 to 100 mM, decreases cell proliferation, induces an accumulation of T47D cells in the S-phase of cell cycle and can induce the cells to fall into apoptosis. The synchronization in the S-phase, with a concomitant decrease of the percentage of cells in the G0-G1-phase, after incubation with azidothymidine concentrations varying between 0.1 and 200 mM, has been described in different human cell lines (Fridland et al 1990;Roskrow & Wickramasinghe 1990;Chandrasekaran et al 1995;Copaceanu et al 1995;Li et al 1997;Viora et al 1997). Out of these cell lines studied, only MCF-7 cells had been included as representative of human breast cancer (Chandrasekaran et al 1995;Li et al 1997).…”