Tissue distribution of DNA adducts in CDF1 mice fed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).
Male and female CDF1 mice were administered a single oral dose of 3 mumol of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and killed 24 h later. DNA was isolated from the livers, lungs, kidneys, colon and forestomach and analysed by 32P-postlabelling for the presence of IQ and MeIQ adducts. Several adduct-enrichment procedures were investigated, including ATP-deficient labelling conditions, butanol extraction and nuclease P1 digestion, and only the ATP-deficient procedure was found to produce the same adduct pattern on polyethyleneimine--cellulose TLC as the standard procedure. Up to nine adduct spots were detected in liver DNA from IQ-treated mice, two of which were not detected in other tissues. The levels of binding in both male and female mice were in the order liver greater than kidney greater than colon greater than forestomach greater than lung. Analysis of DNA from MeIQ-treated mice revealed the presence of up to seven adducts, one of which was detected in liver but not in other tissues. The relative order of DNA binding was kidney greater than liver greater than or equal to colon greater than forestomach greater than lung. As dietary feeding of IQ induces liver, lung and forestomach tumours, and MeIQ induces liver and forestomach tumours in this mouse strain, these binding levels do not correlate with the susceptibility of the organs to carcinogenesis induced by these compounds; the results may indicate the importance of additional factors in determining organ specificity of carcinogenicity.
Hall
M
M
Chester Beatty Laboratories, Royal Cancer Hospital, London, UK.
Shé
M N
MN
Wild
D
D
Fasshauer
I
I
Hewer
A
A
Phillips
D H
DH
D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000493:pharmacokinetics*; D002855:Chromatography, Thin Layer; D004247:DNA / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010761:Phosphorus Radioisotopes; D011804:Quinolines / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002273:Carcinogens; D010761:Phosphorus Radioisotopes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline