Interactions between Radiation and One-Carbon Metabolism

Round 1

Reviewer 1 Report

In this review, authors have discussed how radiation can interact and affect one-carbon metabolism leading to metabolic reprogramming. The authors have suggested that understanding of these interactions can result in identification of new therapeutic targets that can be combined with radiation therapy (RT) to augment its effects against cancer. The review is comprehensive, however, there are few suggestions:

1. Most of the effects described in the review are mediated by total body irradiation (TBI). However, for solid cancer treatment, RT is given locally to the tumor. Therefore, the relevance of the changes induced by TBI and one-carbon metabolism for cancer therapy are not very clear from the review. These effects appear to be more relevant for development of strategies for radiation protection. Therefore, the review will significantly improve if effects of focal irradiation versus TBI are described more clearly and the corresponding implications are accordingly discussed. The conclusions will need to be modified accordingly.
2. Addition of a figure that describes the effects of the RT on various one-carbon metabolism related pathways/cycles (Figure 1 provides only an overview) will significantly help the readers in understanding the interaction of radiation with one-carbon metabolism and subsequent metabolic rewiring. A table describing the effects on the biological outcomes/modifications after irradiation through changes in one-carbon metabolism can also be provided.

In addition, minor concerns and suggestions are:

1. Figure 1: It will be good to add additional substrates needed for the reactions where possible, ex, ATP (for MAT2A) and serine (for SHMT).
2. It is important to identify the type of radiation used, ex line 91: 10 KGy dose is using electron beams.
3. Line 10: Remove “and” after interactions; line 166: add “cancer” after gynecological; line 299: methylation “of” H4-Lys20…

Author Response

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Reviewer 2 Report

The manuscript titled “Interactions between radiation and one-carbon metabolism” by Korimerla and Wahl provides a comprehensive overview of the basic biology of metabolic pathways and delineates how they affect radiation response. Citation of in vitro studies as well as clinical trials that are being conducted will draw interest from translational biologists among other readers of this journal.

Minor comment:

1. The discussion on methotrexate interaction with radiation is rather brief. Expansion on the available evidence of toxicity in both in vitro and patient data will be helpful. 

Author Response

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