Demonstration of Vincristine Resistance in Primary Intestinal Neoplasms in the Rat by the 'post-metaphase Index'

Overview

Journal Br J Cancer

Specialty Oncology

Date 1985 Oct 1

PMID 4063135

Citations 2

Authors

P Ince

K J Finney

D R Appleton

J P Sunter

A J Watson

Affiliations

Soon will be listed here.

Abstract

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 less than 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.

Citing Articles

Verapamil increases the sensitivity of primary human colorectal carcinoma tissue to vincristine.

Ince P, Appleton D, Finney K, Sunter J, Watson A Br J Cancer. 1986; 53(1):137-9.

PMID: 3947510 PMC: 2001478. DOI: 10.1038/bjc.1986.19.

Verapamil sensitizes normal and neoplastic rodent intestinal tissues to the stathmokinetic effect of vincristine in vivo.

Ince P, Appleton D, Finney K, Moorghen M, Sunter J, Watson A Br J Cancer. 1988; 57(4):348-52.

PMID: 3390371 PMC: 2246558. DOI: 10.1038/bjc.1988.80.

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