Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'
| Autor: | Alexander J. Watson, J P Sunter, Paul G. Ince, K J Finney, D R Appleton |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Male
Cancer Research Vincristine Pathology medicine.medical_specialty Intestinal Neoplasm Drug Resistance Mitosis Cell Count Biology In vivo Intestinal Neoplasms medicine Dimethylhydrazine Animals Intestinal Mucosa Metaphase Anaphase Dimethylhydrazines Dose-Response Relationship Drug Rats Inbred Strains In vitro Rats Oncology Mitotic Figure Cancer research Research Article medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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