Hyperplasia of mouse duodenal crypts and its control by NK cells during the initial phase of DMH carcinogenesis

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Abstract
The possible regulatory role of NK cells on early events in chemical carcinogenesis remains undefined. The present study examined whether NK cells control 1, 2-dimethylhydrazine (DMH)-induced hyperplasia of the duodenal crypt in CD, mice. Mice receiving chronic DMH treatment showed a dose-dependent hyperplasia confined to the proliferative zone, with a parallel increase in mitotic and 3H-TdR-labelled cells and significant suppression of splenic NK activity. Complete ablation of splenic NK activity with anti-asialo GM-1 antibody (αAGM-1) treatment slightly enhanced hyperplasia. Halving of the DMH dose for 2 weeks led to regression of hyperplasia, which was totally prevented by αAGM-1 treatment. The αAGM-1 treatment alone did not influence crypt size in normal mice. Finally, a stimulation of NK activity with Poly I:C treatment in DMH-treated mice caused regression of the DMH-induced hyperplasia. Our results suggest that hyperplastic cells with possible genetic alterations induced by the carcinogen express target structures for NK cells, but that simultaneous carcinogen-induced suppression of NK activity hampers their containment, allowing progression of hyperplasia to neoplasia, possibly owing to additional genetic changes.