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. 1985 Oct;52(4):599–605. doi: 10.1038/bjc.1985.232

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

P Ince, K J Finney, D R Appleton, J P Sunter, A J Watson
PMCID: PMC1977255  PMID: 4063135

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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