Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

Round 1

Reviewer 1 Report

This paper presents highly relevant data that can be used in the radiation-induced cardiovascular disease research.

Author Response

Dear reviewer, 

We (the authors) would like to thank you for spending your valuable time to read and comment on our submitted manuscript. We appreciate your positive attitude towards our work.

Reviewer 2 Report

This is an interesting and well-studied manuscript.  The authors did an excellent job identifying parts of the IGF-1 signaling pathway that are differentially altered in decedent and surviving animals of 2 strains of irradiated mice.  The work is important and should be published; however, there are some questions and minor revisions that are requested.  These are outlined in the attached pdf markup.  I recommend that this manuscript be accepted with minor revisions.

Comments for author File: Comments.pdf

Author Response

Dear reviewer,

We would like to thank you cordially for your efforts in reviewing our manuscript and providing valuable comments to improve its quality.

We have tried to address all your comments and have incorporated those changes in the revised manuscript. We also provide our response for the questions which you had encountered during the review process.

Below please find our response to your questions and comments.

Line 99: Do you have a reference documenting this statement?  A reference is added.

Line 106 why weren't females studied? The males-only were used since we wanted to avoid any contributions from the effects of cycling sex hormones in this study. Another reason we used males was owing to the fact that including female mice from two different strains and collecting samples from survivor and decedent animals requires substantial personnel and funding resources which were lacking in our study. However, in an ongoing study, we have used adult male and female mice (C57/Bl6 strain) and we will publish those data in the near future.

Line 114: sham-irradiated? We added the revision to the methods.

Line 132: since animals may have died at different times post-irradiation, this could have an impact on these findings.  Yes, it is well possible that time points of moribundity could have an effect of the measured criteria but since decedent mice were euthanized according to the same endpoint criteria (scoring sick animals health criteria) and in our analyses we used the mice randomly from the pool of decedent mice and all showed similar outcomes with small standard deviations during the analyses, it shows that timing after radiation should have nominal to no effects on the tested criteria. Please if you have any ideas or suggestions to improve addressing this matter, we would appreciate to learn them.

Line 174: does each lane on the Western blot represent a representative single animal or a pooling of samples? The WB lanes each represent samples from single animals.

Lines 179-181: We modified this sentence.

Lines 295-308: This paragraph is added to the concluding section of the discussion.

Lines 343-349: This sentence is way too long - recommend splitting into 2 or 3 sentences.  It is difficult to follow the train of thought as it is now. We shortened the long sentence and rewrote this sentence.

Lines 355-359: Another very long sentence.  Recommend splitting into two. We split this sentence.

382-385. another too-long sentence - recommend removing the word "though" and splitting into two after"C3H/HeN hearts" We rewrote this section.

398: The geometry of radiation was bilateral and is added to methods.

Line 401: Yes midline dose is added to the methods section.

Line 402: Please see line 414, we used Isoflurane

Line 406: We added the relevant text to the Material and Methods section. Sham animals were loaded into Plexiglas® chambers but did not receive any radiation doses during the duration of the irradiation.

Line 496: Additional abbreviations were added.

FYI, all the minor comments and grammatical changes have been addressed in the revised version of the manuscript.