Journal of Applied Physiology, Vol 59, Issue 4 1110-1116, Copyright © 1985 by American Physiological Society
Effects of hyperoxia on DNA synthesis in cultured porcine aortic endothelial cells
A. Clement, U. Hubscher and A. F. Junod
The mode of action of hyperoxia on the inhibition of DNA synthesis from
thymidine (dThd) was studied in primary cultures of porcine aortic
endothelial cells (EC) at confluence. A significant effect of hyperoxia on
dThd uptake was detected only after a 48-h exposure to 95% O2. On the other
hand, decrease in dThd kinase activity was already observed after a 12-h
exposure, and the time course of its reduction followed closely that of the
inhibition of dThd incorporation into DNA. The incorporation of dThd
triphosphate into DNA in permeabilized EC was unaffected by hyperoxia.
Determination of DNA alpha- and beta-polymerase activities showed that
hyperoxia reduced the activity of the alpha-polymerase and increased that
of the beta-polymerase. We conclude that most of the O2 effects on DNA
synthesis from dThd can be attributed to dThd kinase inhibition. The
increased activity of DNA beta-polymerase, an enzyme involved in DNA
repair, also supports the view that hyperoxia could damage DNA.
