Study of kinetics of epithelial cell populations in normal tissues of the rat's intestines and in carcinogenesis

Pozharisski, Kazymir M.; Klimashevski, V.F.; Гущин, В.А.

doi:10.1016/s0232-1513(82)80067-4

Cited by 5 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation suggests that the tight modulation of intestinal cell production to periods of lesser or greater nutrient intake are disturbed in the aging rat and result in lessened control of cell production and further impaired cytokinesis. Indeed, the pattern of crypt proliferating cells outside of the normal crypt proliferating zone that was seen in aging refed rats resembles phase-1 lesions in a two-phase model of colon cancer production (20) and changes described in small and large intestine following administration of the carcinogen dimethylhydrazine (21).…”

Section: Resultsmentioning

confidence: 96%

Altered controls of proliferation in proximal small intestine of the senescent rat.

Holt

Yeh

Kotler

1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The proximal small intestine responds to starvation by rapidly reducing crypt cell proliferation rate and villus cellularity and to resumption of food intake (refeeding) by abruptly increasing proliferation and the number of villus epithelial cells. We show that villus cellularity responds to starvation and refeeding similarly in young and aging animals. However, as compared to young animals, senescent rats showed increased basal DNA synthetic activity, starvation resulted in a smaller decrease in DNA labeling of crypt cells, and refeeding produced an abrupt broadening of the proliferative zone in older animals without concomitant increased numbers of villus cells. Such altered crypt proliferative responses resemble precancerous changes seen in the colon and the aberrant proliferation found in both small and large intestine after administration of the carcinogen dimethylhydrazine.

show abstract

Section: Resultsmentioning

confidence: 96%

Altered controls of proliferation in proximal small intestine of the senescent rat.

Holt

Yeh

Kotler

1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Biological Markers Of Cell Proliferation And Differentiation In Human Gastrointestinal Diseases

Lipkin

Higgins

1988

Advances in Cancer Research

View full text Add to dashboard Cite

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'

Ince¹,

Finney²,

Appleton³

et al. 1985

Br J Cancer

View full text Add to dashboard Cite

Summary A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P<0.001).The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%.Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.Certain drugs, including the Vinca alkaloids and colcemid, have the ability to arrest dividing cells during the mitotic process, by inhibition of microtubular polymerisation in the formation of the mitotic spindle. The resulting 'arrested metaphase' mitotic figures are readily recognisable and provide one approach to the determination of indices of cell proliferation by morphological means, the so-called stathmokinetic experiment. In conventional cellkinetic studies a large dose of the stathmokinetic agent is used in order to arrest all cells entering mitosis, and at full arrest no mitotic figures appear as anaphases or telophases. The rate of accumulation of the dividing cells then gives the cell birth rate (Tannock, 1967;Steel, 1977).In a recent stathmokinetic study of human colorectal carcinoma grown in organ culture Pritchett et al. (1982) showed that tumours required a sixfold larger dose of vincristine to achieve full metaphase arrest than did non-neoplastic mucosa from the same resection specimen. This in vitro observation mirrors the disappointing clinical experience of vincristine treatment of bowel cancer. Much current interest relates to the biochemical, pharmacological and genetic basis of the observed resistance of cancer cells to chemotherapeutic agents. In the case of resistance to the Vinca alkaloids there is an association with the pleiotropic multidrug resistance phenotype (Ling et al., 1983) involving the cell surface glycoprotein P180 (Garman et al., 1983). In several studies using cell lines of both rodent and human origin, in which Correspondence: P. Ince.

show abstract

Study of kinetics of epithelial cell populations in normal tissues of the rat's intestines and in carcinogenesis

Cited by 5 publications

References 12 publications

Altered controls of proliferation in proximal small intestine of the senescent rat.

Altered controls of proliferation in proximal small intestine of the senescent rat.

Biological Markers Of Cell Proliferation And Differentiation In Human Gastrointestinal Diseases

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'

Contact Info

Product

Resources

About