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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.

The radiosensitivity as measured by LD50/6 or LD50/30 of the F1 hybrid B6CF1 (C57BL/6 X BALB/c) is similar to that of C57BL/6 mice but markedly different from BALB/c. The LD50/6 for BALB/c mice was about 8.8 Gy compared to 16.4 Gy for the B6CF1. The difference in LD50/6 between the parent strains or between BALB/c and the F1 hybrid could not be explained by any differences in crypt cell number, cell cycle time, or transit time. Likewise, the observed differences in the LD50/6 do not appear to result from marked differences in the radiosensitivity of marrow stem cells (CFU-S) since the D0's for the three genotypes of mice were similar. Also, there were no apparent differences in the red blood cell contents of several enzymes associated with antioxidant defenses. The microcolony assay was used to determine the D0 for the crypt clonogenic cells and the D0 values for 60Co gamma rays were about 0.8 Gy for BALB/c mice and 1.4 Gy for B6CF1 mice. However, the D0 values for JANUS fission neutrons were similar; 0.6 Gy for the BALB/c mice and 0.5 for the B6CF1 mice. A comparison of clonogenic cell kinetics, using prolonged colcemid block to distinguish between slowly and rapidly cycling cells suggest that, normally, the stem cells are slowly cycling in both the BALB/c and the B6CF1 hybrid. However, the stem cells of the B6CF1 appear to go into rapid cell cycle more rapidly than those of the BALB/c following irradiation or prolonged colcemid treatment. The more rapid recovery in intestinal epihelial cell production in the B6CF1 hybrid after irradiation may provide an increased mucosal barrier and may, in part, explain the difference in the response to radiation compared to that in the BALB/c.

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