Abstract

The lack of a sufficient research base is the reason for the ongoing discussion regarding the genotoxic effect of magnetic field (MF) exposure on mammalian cell cultures. Chinese hamster ovary (CHO) suspension-type cells, which are widely used for biopharmaceutical production, are potentially subjected to an increased MF when cultivated in bioreactors equipped with bottom-placed magnetically coupled stirring mechanisms. The main challenge for conducting research in this field remains the availability of a suitable experimental setup that generates an appropriate MF for the raised research question. In the present study, a simple and cost-effective experimental setup was developed that generated a static MF, similar to what has been modeled in large-scale bioreactors and, at the same time, was suitable for experimental cell cultivation in laboratory conditions. The measured maximum magnetic flux density to which the cells were exposed was 0.66 T. To assess the possible genotoxic effect, cells were continuously subcultivated in laboratory petri dishes for a period of 14 days, corresponding to a typical duration of a biopharmaceutical production process in a conventional fed-batch regime. The genotoxic effect was assessed using the cytokinesis-block micronucleus assay with fluorescent staining. Results showed that a 0.66-T static MF exposure had no significant long-term effect on cell viability and chromosomal damage but demonstrated a short-term effect on cell apoptosis. Significant increase in nuclear bud formation was observed. These findings may encourage other researchers in future studies investigating cellular responses to MF exposure and contribute relevant data for comparison.

Highlights

  • The magnetic field (MF) influence on various biological systems has been widely reviewed (Dini and Abbro, 2005; Miyakoshi, 2005; Ghodbane et al, 2013; Zhang X. et al, 2017), it is challenging to find sufficient evidence when a case study with defined MF parameters is presented

  • The effects of DNA damage to Chinese hamster ovary (CHO)-S suspension cell line after exposure to 0.66-T static MF were evaluated by performing the cytokinesis-block MN (CBMN) assay

  • This study investigated the genotoxic effect of a static MF similar to those found in bioreactors equipped with bottom-placed magnetically coupled stirring mechanisms (0.66 T) that are used for the industrial production of biopharmaceuticals

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Summary

Introduction

The magnetic field (MF) influence on various biological systems has been widely reviewed (Dini and Abbro, 2005; Miyakoshi, 2005; Ghodbane et al, 2013; Zhang X. et al, 2017), it is challenging to find sufficient evidence when a case study with defined MF parameters is presented. The MF exposure is discussed in the context of MF-initiated stirring mechanisms (agitators) in bioreactors, as the cells can directly interact with the MF in the case of bottom-placed magnetic coupling mixers. They are made of the drive and driven magnets interacting at the end of an agitator shaft (Liu, 2013; Stanbury et al, 2017). This technology is easier to clean and sterilize and could be useful for mammalian cell cultivation as they require the highest level of sterility, compared to other industrial microorganisms (Kretzmer, 2002)

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