Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring.

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.

Cell renewal in noncornified and cornified buccal epithelium in the rabbit.

This study was undertaken to compare some aspects of cell renewal in the noncornified and cornified epithelia that are juxtaposed in the buccal mucosa of the rabbit. Specimens were analyzed by autoradiography and scintillation counting at various times after the injection of tritiated thymidine or triated proline. In the noncornified epithelium, the labeling index in the proliferative compartment at 1 hr was 15.5%; in the entire cell population, it was 5.8% at 1 hr, 10.4% at 24 hr, and 20.2% at 72 hr. The leading edge of labeled cells reached the surface by 96 hr. In the cornified epithelium, the labeling index in the proliferative compartment was 8.7% at 1 hr; in the entire nucleated cell population, it was 4.2% at 1 hr, 9.2% at 24 hr, and 12.1% at 96 hr. The leading edge of labeled cells reached the stratum corneum by 96 hr and the surface by 144 hr. It was concluded that renewal occurs at a more rapid rate in the noncornified than in the cornified epithelium under study.

Cytotoxic effects of colcemid or high specific activity tritiated thymidine on clonogenic cell survival in B6CF1 mice.

High specific activity tritiated thymidine (HSA-[3H]TdR) and colcemid were given in cytotoxic doses and regimens to B6CF1/Anl mice. The number of cells per intestinal crypt was reduced by the S-phase-specific (HSA-[3H]TdR and the metaphase blocking and cytotoxic effect of multiple injections of colcemid. In 50-day-old mice, the cytotoxic effect of multiple injections of colcemid reduced both the number of cells per crypt and the clonogenic cell survival. However, the number of surviving intestinal clonogenic or stem cells, assayed by the microcolony technique, did not change in 110--130-day old mice. These data suggest that most of the cells at risk from these cytotoxic agents are not clonogenic in adult 110--130-day old mice but are the cells in amplification division. However, since the stem cells of young mice are more susceptible to colcemid, they are apparently in a more rapid cell cycle than those of older mice. The clonogenic cell survival measured in 110--130-day old mice after a single radiation dose of 14 Gy (1400 rad) responded in a non-linear way to increasing time of continuous colcemid cytotoxicity. These data suggest that the intestinal stem cells can respond to amplification compartment cell death by a shortening of their cell cycle and thus, over time, the number of stem cells at risk to colcemid cytotoxicity increases.