Mutagenesis of Mouse Intestine in Vivo Using the Dlb-1 Specific Locus Test: Studies with 1,2-Dimethylhydrazine, Dimethylnitrosamine, and the Dietary Mutagen 2-Amino-3,8-dimethylimidazo[4,5-/]quinoxaline1
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چکیده
The ability of three model carcinogens, 1,2-dimethylhydrazine, di methylnitrosamine, and 2-amino-3,8-dimethylimidazo|4,5-/]qiiinoxaline, to induce mutation in a novel in vivo assay in mouse intestine has been examined. The assay is based on mutations at the Dlb-1 locus which determines the tissue specific pattern of expression of the binding site for the lectin Doltchos bifloras agglutinin. In C57BL/6J x SWR F, mice Dlb-1 mutants are recognized as clones of epithelial cells not staining with a peroxidase conjugate of I), hifloras agglutinin. Chronic adminis tration of 1,2-dimethylhydrazine (20 mg/kg/week s.c. for 10 weeks) induced Dlb-1 mutants, whereas administration of a single dose did not. Similarly, chronic dimethylnitrosamine treatment p.o. (0.001% in drink ing water for 8 weeks) induced l>lh-/ mutants, but acute administration did not. In contrast, neither chronic nor acute treatment of the mice with 2-amino-3,8-dimethylimidazo[4,5-/)quinoxaline induced l)lh-l muta tions. The activities of 1,2-dimethylhydrazine, dimethylnitrosamine, and 2-amino-3,8-dimethyIimidazo(4,5-/|quinoxaline in the Dlb-1 assay more accurately reflect their carcinogenic potential than do many in vitro bioassays.
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