Distribution and elimination of [2-14C]amino-3,8-dimethylimidazo [4, 5-f] quinoxaline in mice. Analysis by whole animal autoradiography.
1. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a potent bacterial promutagen and carcinogen, formed when beef is cooked. In mammals, MeIQx is metabolized and activated by liver enzymes, but induces tumours in both hepatic and extrahepatic tissues. 2. Intravenous administration of [14C]MeIQx and whole animal autoradiography has been employed to examine the disposition of MeIQx. Within 10 min, radiolabel was distributed throughout body tissue. Liver levels of radioactivity rapidly rose and remained elevated in comparison to other tissues, throughout the period of study (4 d). 3. At early time points radioactivity accumulated in the stomach, kidney and salivary glands then later in the intestine. Radioactivity was rapidly eliminated from the majority of tissues although did persist in liver and intestines throughout the duration of the study, probably due to covalently bound material. No radioactivity could be detected in the central nervous system, thus neither MeIQx nor its metabolites cross the blood-brain barrier to any significant extent. 4. The rapid elimination of radioactivity from the tissues is in good agreement with the time course of excretion of MeIQx. Irrespective of the route of administration (i.v., i.p., p.o.), a substantial proportion of the labelled material is excreted within 24 h and is present in both urine and faeces in similar quantities. 5. Thus MeIQx is extensively bioavailable, is distributed throughout body tissue and, although the majority is quickly cleared, some remains bound to liver and intestine.
Gooderham
N J
NJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, UK.
Soames
A
A
Rice
J C
JC
Boobis
A R
AR
Davies
D S
DS
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011810:Quinoxalines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline