English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of responses and no clear pathway has yet emerged, especially as little is known about the capacity of this agent to enhance DNA damage in normal, untransformed cells. Continuous exposure to commonly used caffeine concentrations (1-5 mM) inhibited the proliferation of normal human fibroblasts (NHFs) in a dose-dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to UVc radiation (20 J m(-2)) or gamma radiation (2.5-8 Gy) led to a 45-60% inhibition of proliferation and protracted accumulation of cells in the G2/M phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase passage, with a resultant delay in G2/M accumulation mimicking a G2/M block override. These results were confirmed by stathmokinetic studies, which showed delayed entry of the cells into mitosis in the presence of caffeine. Our data demonstrate that caffeine primarily inhibits replicative DNA synthesis and suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of radiation by intervening in DNA repair rather than by overriding the G2/M block.

Caffeine does not cause override of the G2/M block induced by UVc or gamma radiation in normal human skin fibroblasts