16, 16-Dimethyl Prostaglandin E 2 Induces Radioprotection in Murine Intestinal and Hematopoietic Stem Cells

Abstract

Exogenous prostaglandins (PGs) have been shown to protect gastrointestinal mucosa, liver, and pancreas from several injurious agents, including the PG inhibitor, indomethacin. Previous studies from this laboratory showed exogenous administration of 16,16-dimethyl (dm) PGE2 also protected mouse intestinal stem cells from radiation injury. The present study extended that observation and demonstrated that PGs given to B6D2F1 mice 1 hr before irradiation increased the shoulder of the intestinal clonogenic cell survival curve. The D0 increased from 1.10 + 0.09 to 1.58 + 0.10 Gy. PGs increased the LD50/6 from 16.3 + 0.41 (95% confidence limits) in controls to 20.25 + 0.55 Gy. The 16,16-dm PGE2 increased the hematopoietic CFU-S survival in a qualitatively similar way; the extrapolation number (n) was increased from 1.03 (0.89-1.20) to 1.40 (1.27-1.54) and the D0 increased from 0.92 (0.87-0.98) to 1.14 (1.10-1.19) Gy. A large number of human tumors secrete a variety of PGs. Our results suggest that those tumors may be, in part, protected from radiation injury.

Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E 2 in radiation damage

“…Prostaglandin E 2 (PGE 2 ), generated from arachidonic acid by cyclooxygenase 1 (COX-1) or COX-2, protects the intestinal epithelium from IR by increasing stem cell survival and diminishing apoptosis (4,5). COX-1 is constitutively expressed and promotes tissue homeostasis.…”

The modulation of radiation-induced damage to pig skin by essential fatty acids

“…In order to resolve whether GLA might act as a radioprotector rather than a BRM these oils were given either up to the time of irradiation only or both before and after irradiation. PGs have been reported to protect against radiation damage (Hanson & Ainsworth, 1985). EFA administration was initiated 4 weeks prior to irradiation to ensure stable EFA levels in the animals before local skin irradiation.…”

Acetylsalicylic acid (ASA) protects the prostaglandin-cAMP-system of human hypernephroma cells against irradiation-induced alterations

“…Initially it was proposed that the augmentation of radioresponse induced by indomethacin could be due to lowering PGs in tumour tissues. The effects of PGs on radioprotection are, however, not clear: some authors reported that PGs might act as radioprotectors (Hanson & Ainsworth, 1985;Walden et al, 1987), whereas others (Milas et al, 1990) proposed an opposite effect.…”

“…Apart from the fact that the mechanisms by which indomethacin potentiates tumour radioresponse are still unclear to date, it appears that an increased tumour response might be achieved by lowering PGs in the tumour. This, however, would imply that PGs are not radioprotective agents as has been suggested by Hanson & Ainsworth (1985) or Walden et al (1987). Milas and coworkers (1990) have also found that potentiation of the tumour radioresponse induced by indomethacin is more significant when it is given after rather than before irradiation.…”