The Labelled Mitoses Curve and the Estimation of the Parameters of the Cell Cycle

Summary.-We have measured mitotic indices and 3H-thymidine-labelling indices for the colonic epithelial tumours induced in rats by the administration of dimethylhydrazine (DMH). The fraction-of-labelled-mitoses (FLM) technique has been used to estimate the duration of the cell-cycle phases.In general, mitotic and labelling indices in the tumours are similar to those in the proliferation zone of the normal crypt epithelium; lesions considered to be least well differentiated on histological grounds appear to have the lowest mean labelling index. Benign tumours and the different types of malignant tumours have mean cell-cycle times about half those of the normal mucosa.

Section: Methodsmentioning

confidence: 99%

Cell proliferation of colonic neoplasms in dimethylhydrazine-treated rats

Sunter¹,

Hull²,

Appleton³

et al. 1980

“…P. SUNTER, 1). R. APPLETON, N. A. WRIGHT AND A. J. WXATSON str-ucted, and the data were analysed by the metlhod of Gilbert (1972). V;inocristinte stuidies. Eighteen animals which had received 24 w^eekly injections of DM1H w<ere given vincristine sulphate (Oncovin, Eli Lilly) by i.p.…”

Section: Methodsmentioning

confidence: 99%

Kinetics of changes in the crypts of the jejunal mucosa of dimethylhydrazine-treated rats

Sunter¹,

Appleton²,

Wright³

et al. 1978

Summary.-When symmetrical 1,2 dimethylhydrazine was administered to rats by weekly s.c. injection, 37% of the animals had developed small intestinal carcinomas after 21-27 weeks. These lesions were largely localized to duodenum and upper jejunum. At the same time there was a diffuse crypt hyperplasia in the jejunum which affected all the treated animals, not just those with neoplasms. This marked hyperplasia was preceded by a modest sustained crypt elongation which was seen soon after DMH injections began.In these hyperplastic jejunal crypts the absolute size of the proliferative compartment was increased, but the growth fraction calculated from labelling studies appeared to fall, probably by reduction in relative size of the proliferating population within the proliferative compartment.No convincing alteration in actual cell-cycle time was observed in the abnormal crypts. There was a slight (25%) increase in cell-production rate in the abnormal crypts.

“…The cell-cycle phase durations calculated from the curves fitted to the whole-crypt FLM data are shown in Table III Table III are the estimates of the coefficient of variation of Tc provided by the Gilbert (1972) programme, and estimates of the theoretical labelling indices. In the calculation of this latter parameter we have assumed a rectangular age distribution, and have compensated for the variability of Tc .…”

Section: Results and Interpretationmentioning

confidence: 99%

Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats

Sunter¹,

Watson²,

Appleton³

1981

Summary.-Administration of 1,2 dimethylhydrazine (DMH) to rats by weekly s.c. injections causes the development of multiple epithelial tumours of the large bowel. These appear to arise as localized dysplastic abnormalities in hitherto apparently morphologically normal crypts. This study was undertaken in order to examine cell proliferation in such apparently normal crypts of DMH-treated animals.A number of proliferative abnormalities are evident, including changes in the size of the crypts, changes in the disposition of proliferating cells within them and reduced cell-cycle times. The nature and the extent of the abnormalities vary from site to site along the length of the bowel, and reflect the vulnerability of the different segments of the bowel, not only to the carcinogenic effects of DMH, but also to short-term toxicity.