Hyperplasia of mouse duodenal crypts and its control by NK cells during the initial phase of DMH carcinogenesis.
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 CD1 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-I antibody (alpha AGM-I) treatment slightly enhanced hyperplasia. Halving of the DMH dose for 2 weeks led to regression of hyperplasia, which was totally prevented by alpha AGM-I treatment. The alpha AGM-I 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.
Department of Anatomy, University of Western Ontario, London, Canada.
G G
GG
Altmann
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Parhar
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Lala
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D004127:Dimethylhydrazines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004379:Duodenal Neoplasms / Q000139:chemically induced / Q000276:immunology*; D004386:Duodenum / Q000473:pathology*; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000502:physiology; D006965:Hyperplasia / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D013997:Time Factors
D002273:Carcinogens; D004127:Dimethylhydrazines; D006028:Glycosphingolipids; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D019813:1,2-Dimethylhydrazine