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WindowsCarcinogen-induced hyperproliferation in rat forestomach associated with alterations in growth factor receptor mRNA levels.
The forestomachs of male Sprague-Dawley rats were exposed to MNNG by oral gavage once a week for up to 12 weeks, or once every four weeks for up to 24 weeks. Forestomachs were examined for the presence of tumors, hyperproliferation, and changes in growth factor receptor mRNA levels. An increase in the mean number of tumors/animal occurred in animals exposed to MNNG for 1 week, 4 weeks, 8 weeks, or 12 weeks. A slight but significant increase in the incidence of hyperplasia was observed in animals exposed for 8 and 12 weeks. Following 24 weeks of MNNG exposure, an increase in the incidence of hyperplasia was observed. Moreover, these animals exhibited an increase in the mean number of hyperplastic lesions/animal. MNNG treatment increased the mean number of cells in the lower portion of the epithelial compartment of the forestomach in animals treated for 8 or 12 weeks. The cell cycle distribution of the lower portion of the epithelium revealed that MNNG exposure for 8 weeks induced a reduction in G1 phase cells, which was associated with an increase in S phase cells. In animals exposed to MNNG for 12 weeks, there was a significant increase in S phase cells, but no change in G1 phase cells. Southern blot analysis showed that MNNG treatment for 12 weeks increased the level of epidermal growth factor receptor mRNA in the lower portion of the forestomach. In contrast, the levels of transforming growth factor alpha and beta mRNAs were not altered. In situ hybridization studies showed that MNNG treatment for 12 weeks was associated with an increase in the level of transforming growth factor alpha mRNA in the lower portion of the epithelium. These results indicate that an increase in the proliferative response of rat forestomach cells to epidermal growth factor is associated with alterations in transforming growth factor alpha and epidermal growth factor receptor mRNA levels. Moreover, an increase in the number of tumor/animal and an increase in the number of hyperplastic lesions/animal are associated with a change in the number of cells in the lower portion of the epithelium that are in the cell cycle, which is associated with an increase in the number of cells in the S phase of the cell cycle.import ‘package:flutter/material.dart’;

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