Intracellular ascorbate is a safe-guard and/or reservoir for plasma vitamin C in prostate cancer patients undergoing radiotherapy

Free Radic Biol Med. 2024 Jan:210:230-236. doi: 10.1016/j.freeradbiomed.2023.11.024. Epub 2023 Nov 29.

Abstract

Prostate cancer (PC) represents one of the most common cancer types worldwide and many patients suffering from this kind of cancer are treated with radiotherapy (RTH). Ionizing irradiation is closely associated with reactive oxygen species (ROS) production and oxidative stress. Over the years the role of vitamin C (VC) in cancer prevention has been highlighted as it may be mediated by its ability to neutralize pro-carcinogenic ROS. However, the debate concerning the presence of VC in blood and its beneficial effect on the survival of cancer patients is inconsistent and controversial. To our best knowledge until recently there have been no studies concerning such a role of intracellular VC (iVC). In the present study, blood and intracellular concentrations of vitamin C were analyzed along with the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), as an established marker of the stress condition, in leukocytes of PC patients during the course of radiotherapy. The level of intracellular vitamin C significantly decreased in PC patients in comparison with the healthy group, while there were no differences in blood VC. It was observed that a sub-group of the PC patients reacted to RTH decreasing VC in leukocytes (group A), while the other sub-group acted the other way round, significantly increasing its level (group B). Under stressful conditions (RTH) leukocytes react in two different ways. Both ways are in good agreement with two well recognized functions, proposed for iVC; it may serve as a save factor, to protect the cellular DNA, increasing its concentration inside the cell (group B), and as a reservoir decreasing the VC level inside leukocytes and releasing VC into the plasma to rescue its physiological level (group A). It was also demonstrated that there was a relationship between the level of 8-oxodG in leukocytes' DNA and the markers of RTH toxicity.

Keywords: 8-oxodG; DNA modifications; Prostate cancer; Radiotherapy; Vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Ascorbic Acid*
  • DNA / metabolism
  • DNA Damage
  • Deoxyguanosine / metabolism
  • Humans
  • Male
  • Oxidative Stress
  • Prostatic Neoplasms* / radiotherapy
  • Reactive Oxygen Species
  • Vitamins

Substances

  • Ascorbic Acid
  • 8-Hydroxy-2'-Deoxyguanosine
  • Reactive Oxygen Species
  • Deoxyguanosine
  • Vitamins
  • DNA