Abstract
The spacial distribution of cell death among the epithelial cells lining the adult mammalian small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (beta particles from tritium, gamma- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. The results, in the form of distributions of dead cells at each cell position, show that each of the various cytotoxic agents tends to act preferentially over a characteristic small range of cell positions. Since cell position is likely to be related to hierarchical cell position within a family tree or cell lineage, each agent tends to act with greatest efficiency on cells at a particular position within the lineage. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Altmann G. G. Morphological effects of a large single dose of cycloheximide on the intestinal epithelium of the rat. Am J Anat. 1975 Jun;143(2):219–239. doi: 10.1002/aja.1001430205. [DOI] [PubMed] [Google Scholar]
- Bjerknes M., Cheng H. The stem-cell zone of the small intestinal epithelium. III. Evidence from columnar, enteroendocrine, and mucous cells in the adult mouse. Am J Anat. 1981 Jan;160(1):77–91. doi: 10.1002/aja.1001600107. [DOI] [PubMed] [Google Scholar]
- Cairns J. Mutation selection and the natural history of cancer. Nature. 1975 May 15;255(5505):197–200. doi: 10.1038/255197a0. [DOI] [PubMed] [Google Scholar]
- Cheng H., Leblond C. P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat. 1974 Dec;141(4):537–561. doi: 10.1002/aja.1001410407. [DOI] [PubMed] [Google Scholar]
- Elmes M. E., Jones J. G. Ultrastructural studies on Paneth cell apoptosis in zinc deficient rats. Cell Tissue Res. 1980;208(1):57–63. doi: 10.1007/BF00234173. [DOI] [PubMed] [Google Scholar]
- Kerr J. F. Shrinkage necrosis: a distinct mode of cellular death. J Pathol. 1971 Sep;105(1):13–20. doi: 10.1002/path.1711050103. [DOI] [PubMed] [Google Scholar]
- Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lu C. C., Meistrich M. L. Cytotoxic effects of chemotherapeutic drugs on mouse testis cells. Cancer Res. 1979 Sep;39(9):3575–3582. [PubMed] [Google Scholar]
- Meistrich M. L., Finch M., da Cunha M. F., Hacker U., Au W. W. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res. 1982 Jan;42(1):122–131. [PubMed] [Google Scholar]
- Potten C. S., Al-Barwari S. E., Hume W. J., Searle J. Circadian rhythms of presumptive stem cells in three different epithelia of the mouse. Cell Tissue Kinet. 1977 Nov;10(6):557–568. doi: 10.1111/j.1365-2184.1977.tb00312.x. [DOI] [PubMed] [Google Scholar]
- Potten C. S., Al-Barwari S. E., Searle J. Differential radiation response amongst proliferating epithelial cells. Cell Tissue Kinet. 1978 Mar;11(2):149–160. doi: 10.1111/j.1365-2184.1978.tb00883.x. [DOI] [PubMed] [Google Scholar]
- Potten C. S., Chwalinski S., Swindell R., Palmer M. The spatial organization of the hierarchical proliferative cells of the crypts of the small intestine into clusters of 'synchronized' cells. Cell Tissue Kinet. 1982 Jul;15(4):351–370. doi: 10.1111/j.1365-2184.1982.tb01053.x. [DOI] [PubMed] [Google Scholar]
- Potten C. S. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature. 1977 Oct 6;269(5628):518–521. doi: 10.1038/269518a0. [DOI] [PubMed] [Google Scholar]
- Potten C. S., Hume W. J., Reid P., Cairns J. The segregation of DNA in epithelial stem cells. Cell. 1978 Nov;15(3):899–906. doi: 10.1016/0092-8674(78)90274-x. [DOI] [PubMed] [Google Scholar]
- Potten C. S., Schofield R., Lajtha L. G. A comparison of cell replacement in bone marrow, testis and three regions of surface epithelium. Biochim Biophys Acta. 1979 Aug 10;560(2):281–299. doi: 10.1016/0304-419x(79)90022-2. [DOI] [PubMed] [Google Scholar]
- QUASTLER H., SHERMAN F. G. Cell population kinetics in the intestinal epithelium of the mouse. Exp Cell Res. 1959 Jun;17(3):420–438. doi: 10.1016/0014-4827(59)90063-1. [DOI] [PubMed] [Google Scholar]
- Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4(1-2):7–25. [PubMed] [Google Scholar]
- Searle J., Lawson T. A., Abbott P. J., Harmon B., Kerr J. F. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. J Pathol. 1975 Jul;116(3):129–138. doi: 10.1002/path.1711160302. [DOI] [PubMed] [Google Scholar]