Covalent binding of [2-14C]2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) to mouse DNA in vivo.
Female BALB/c mice were administered intragastrically with equimolar amounts of either [2-14C]2-amino-3,8-dimethyl-[4,5-f]quinoxaline (MeIQx) or 2-acetylamino[9-14C]fluorene (2AAF). DNA was isolated from tissues of mice killed either 6 or 24 h after administration. Analysis of lvier DNA nucleotide digests by HPLC analysis revealed that all of the radioactivity was attributable to adduct formation. The specific activities of DNA samples were converted to covalent binding indices (CBI, mumol adduct per mol DNA nucleotides/mmol chemical applied per kg animal body weight). CBI values of 25 and 9 were determined for 2AAF and MeIQx in the livers of mice killed 6 h after dosing. The values were in general agreement with the moderate carcinogenic potency of these compounds. The specific activities of DNA preparations obtained from the kidneys, spleens, stomachs, small intestines and large intestines of mice treated with MeIQx and killed 6 h after dosing were 5- to 35-times less than those obtained with the liver. DNA isolated from the lungs (a target organ for MeIQx tumorigenicity) of MeIQx-treated mice was not radiolabelled at the limit of detection (CBI less than 0.3). With the exception of the gastrointestinal tract, the specific activities of DNA samples isolated from mice killed 6 h after administration were higher than those from mice killed after 24 h.
Alldrick
A J
AJ
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach, Switzerland.
Lutz
W K
WK
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009153:Mutagens / Q000378:metabolism*; D011810:Quinoxalines / Q000378:metabolism* / Q000493:pharmacokinetics; D011865:Radioisotope Dilution Technique; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004247:DNA