Reduction of (1- 13 C)-dehydroascorbic acid to (1- 13 C)-ascorbic acid is not correlated to glutathione in a treatment response model of murine lymphoma in vivo
Kerstin N Timm 1,2 , Mikko I Kettunen 1,2 , De E Hu 1,2 , Tiago B Rodrigues 1,2 , Timothy J Larkin 1,2 , Irene Marco-Rius 1,2 , and Kevin M Brindle 1,2
Department of Biochemistry, University of
Cambridge, Cambridge, Cambridgshire, United Kingdom,
Research UK Cambridge Institute, University of
Cambridge, Cambridge, Cambridgshire, United Kingdom
Hyperpolarized [1-13C]-dehydroascorbic acid (DHA), the
oxidized form of vitamin C, can be used as a magnetic
resonance marker of redox state in vitro and in vivo.
What limits the reduction of hyperpolarized [1-13C]-DHA
to [1-13C]-ascorbic acid (AA) in vivo and hence which
metabolic process it directly reports on is still poorly
understood. We treated EL4 tumor bearing mice with the
topoisomerase inhibitor etoposide and showed that the
reduction rate of hyperpolarized [1-13C]-DHA in vivo is
highly variable, which was not correlated with
intracellular glutathione levels. This suggests
contribution of other factors such as NADPH from the
pentose phosphate pathway.
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