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-f]quinoxaline.
The ability of three model carcinogens, 1,2-dimethylhydrazine, dimethylnitrosamine, and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 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 expressio of the binding site for the lectin Dolichos biflorus agglutinin. In C57BL/6J x SWR F1 mice Dlb-1 mutants are recognized as clones of epithelial cells not staining with a peroxidase conjugate of D. biflorus agglutinin. Chronic administration 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 drinking water for 8 weeks) induced Dlb-1 mutants, but acute administration did not. In contrast, neither chronic nor acute treatment of the mice with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline induced Dlb-1 mutations. The activities of 1,2-dimethylhydrazine, dimethylnitrosamine, and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the Dlb-1 assay more accurately reflect their carcinogenic potential than do many in vitro bioassays.
Winton
D J
DJ
Department of Pathology, University of Cambridge, United Kingdom.
Gooderham
N J
NJ
Boobis
A R
AR
Davies
D S
DS
Ponder
B A
BA
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002874:Chromosome Mapping; D004127:Dimethylhydrazines / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D011810:Quinoxalines / Q000494:pharmacology / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects
D002273:Carcinogens; D004127:Dimethylhydrazines; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D019813:1,2-Dimethylhydrazine; D004128:Dimethylnitrosamine