EFFECT OF TOTAL-BODY X-RADIATION FROM NEAR THRESHOLD TO TISSUE-LETHAL DOSES ON THE SMALL BOWEL EPITHELIUM OF THE RAT. I. CHANGES IN MORPHOLOGY AND RATE OF CELL DIVISION IN RELATION TO TIME AND DOSE

Technical Report · Thu Jan 23 04:00:00 EST 1958

OSTI ID:4276371

Williams, Jr, R B; Toal, J N; White, J; Carpenter, H M

6 < : < 8 5 5 9 8 5 7 8 8 7cine, of epithelial cells lining the crypts of the small bowel of control, male, Sprague-Dawley rats weighing 200 plus or minus 25 grams, is about 45 minutes. The percent of . cells in division is 2.5. The intermitotic time is approxi- mately 30 hours. In normal animals, a constant total epithelial cell population divided equally between crypts and villi, and a constant rate of division in the crypts, would result in a complete turnover of the epithelium in approximately 60 hours. Following x irradiation differential effects upon epithelial cells in the crypts have . been demonstrated which consist of an initial drop in mitotic activity, acute cell destruction, absortive mitotic recovery, prolongation of interphase, and final recovery with overshooting. Acute destruction and an abortive mitotic recovery are responses of cells presumed to be in late interphase at the time of irradiation. Acute cell death is characterized by vacuolization, rupture and fragmentation of the nucleus with the number of cells involved increasing with dose but decreasing in proportion to dose. The number of cells acutely destroyed appears to vary inversely with the number undergoing an abortive mitotic recovery. On the basis of graphical integrations the stem cells involved in these effects are estimated to occupy normally about 8 hours of the intermitotic period. Both acute destruction and an initial delay in division appear to be involved in the shapes of the abortive recovery curves. Overshooting in mitotic activity above control levels does not occur to a significant degree during the abortive recovery. Prolongation of interphase is attributed to stem cells presumed to be in early interphase at the time of irradiation. This prolongation of interphase continues to increase as the dose is raised. Recovery may be delayed for periods of time equivalent to several normal interphases. Final recovery appears to involve a decrease in the intermitotic time of surviving stem cells. This provides a mechanism for replacement of those stem cells that have been acutely destroyed, an explanation for the sustained overshoot in mitotic activity observed during recovery, and a restoration of the normal age relationships of epithelial cells lining the crypts and villi. Puring final recovery sustained overshooting of mitotic activity occurs and increases in magnitude up to doses of 450 r, while the number of cells undergoing acute destruction also increases. There is an increase in weight of the entire small intestine above control levels, the extent of which is directly related to the degree of overshooting in mitotic activity. As the dose of x rays increases above 450 r an increasing number of crypts fail to recover at all, thus reducing the total number of cells involved in the overshoot. Acute cell destruction and differentiation and death, in lieu of division, occur earlier and involve greater numbers of stem cells as the dose of x rays is increased. On the other hand, the abortive rise in mi totic activity and final sustained recovery occur later as the number of roentgens is increased. A tissue-lethal dose of radiation does not result in the acute destruction of the majority of cells involved in the continual replacement of the small bowel epithelium. However, a permanent inhibition of division occurs. After such doses the bulk of the stem cells undergo differentiation and survive for several days, the effect being somewhat analogous to sterilization. This action of x irradiation may be due to the complete destruction of some compound that stem cells in early interphase are synthesizing during their progress towards division. Lesser degrees of destruction lead to the dose dependent prolongation of interphase observed. These effects of x irradiation upon stem

• Research Organization: Naval Medical Research Inst., Bethesda, Md.; National Cancer Inst., Bethesda, Md.
• NSA Number: NSA-13-005226
• OSTI ID: 4276371
• Report Number(s): NM-62-02-00.02.01
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

ALKALOIDS
ANIMALS
BIBLIOGRAPHY
BIOLOGY AND MEDICINE
BODY
COLCHICINE
CONTROL
CYTOLOGY
DIAGRAMS
DRUGS
ENVIRONMENT
HORMONES
INTESTINE
LETHAL DOSE
MITOSIS
OXYGEN
RADIATION DOSES
RADIATION EFFECTS
RATS
RECOVERY
SEX
WEIGHT
X RADIATION