The variability of trace and bulk metals in culture media may subsequently lead to unpredictable behavior in CHO cell culture. In the fields of human health and nutritional sciences, trace metal deficiencies and surpluses have shown to significantly impact mechanisms oxidative stress in mammalian cells. However, the relationship between cellular metal consumption, nutrient metabolism, and oxidative stress interplay in CHO cell culture remains unclear. In this study, the total intracellular and mitochondrial trace metal content of CHO cells supplied with various treatments of zinc and iron content in culture media and isolated mitochondria were assessed via inductively coupled plasma mass spectrometry (ICP-MS). Mechanisms of oxidative stress—peroxidase activity, superoxide dismutase activity, and hydroxyl radical generation, as well as mitochondrial membrane potential were also surveyed. Current results indicate that intracellular metal acquisition is most active during lag phase, after which minimal differences in cellular metal consumption are noticed. Apoptotic cultures operating under either a trace metal deficiency or overabundance also exhibit higher specific production of both glutamate and ammonium comparatively. Peroxidase activity and total superoxide dismutase activity are also optimized by these trace metal treatments, demonstrating cellular capability to combat oxidative stress under varying metal conditions. Moreover, hydroxyl radical generation and membrane potential are significantly impacted by mitochondrial iron content as well while enhancing mAb specific productivity. Here, we offer new insight into the impact of trace metal variations in culture media on overall CHO culture performance.

Trace metal variability in culture media can impair CHO culture performance by enhancing mechanisms of oxidative stress

ACS Fall 2020 Virtual Meeting

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