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Caffeine is known to overcome G2/M (and possibly other types of) cell cycle arrest through its effects on DNA repair machinery and is used as a positive control in studies of cell cycle arrest. In this paper, for example, researchers use concentrations of caffeine in the 1-4 mM range to overcome nocodazole-mediated arrest. Is this a physiologically relevant concentration?

I found a lot of interesting caffeine data including the LD50 (estimated to be around 150-200 mg/kg) but have not been able to turn up any good numbers on reasonable concentrations that might be found in a human.

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  • $\begingroup$ To make sure I understand your question right: You are looking for the physiologically occurring caffeine concentrations in the human body? For example after consuming coffee? $\endgroup$ – Chris Oct 23 '14 at 20:14
  • $\begingroup$ Yes, that is correct $\endgroup$ – Luigi Oct 23 '14 at 23:28
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Let's figure it out. Suppose an adult with an average blood volume of 5 L (5000 mL) drinks a cup of strong coffee with 100 mg of caffeine in it. Given caffeine's formula weight of 194.19 g/mol, and assuming 100% of the caffeine is in the blood stream, its concentration (from this awesome calculator page from Graphpad, the makers of Prism) would be approximately 103 µM, or 10-40 times less than what's being used in the experiments you cite.

Of course, this is overcoming drug-mediated cell cycle arrest, so its possible that a lower concentration is needed to jump-start physiologically-arrested cells.

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