The Metabolic Capabilities Of Cell Culture Models

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Uncertainty about the metabolic capabilities in cell culture models is one of the challenges in the utilization of in vitro models in toxicity screening. We have demonstrated that metabolism of phthalate diesters is occurring in our model of male testes development (3D-TCS), as evidenced by detection of monoester metabolites in cell lysate and cell media. Phthalates were metabolized at different rates over time and levels of metabolites ranged from <0.1%-13% of initial concentration of phthalate parent compound. The phase I reaction of phthalate metabolism (see Figures 1. a-c) produces the monoester metabolites and is catalyzed by a class of enzymes called lipases. These enzymes also play important roles in lipid metabolism and in male reproductive development (Holst et al. 1994; Chung et al. 2001). The rate of metabolism observed (in units of picomoles/mg of protein/minute) for DBP and DEP was within the range of reported rates for lipase activity in rat testes and for human testes subcellular fractions, while the rate of metabolism of DEHP was about one-sixth of the lowest of the reported rates (see Table 1). Interestingly, the rates of monoester metabolite formation across the three phthalates appeared to follow a trend similar to that reported by Lake et al., who observed in rat and human intestinal preparations, that phthalates with shorter alkyl side chain length were metabolized at a faster rate compared to those with longer side chains. For example, DBP was
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