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 equimolaramounts of either [2-¹⁴C]2-amino-3,8-dimethyl-[4,5-f]quinoxaline(MeIQx) or 2-acetylamino[9-¹⁴C]fluorene (2AAF). DNA was isolatedfrom tissues of mice killed either 6 or 24 h after administration.Analysis of liver DNA nucleotide digests by HPLC analysis revealedthat all of the radioactivity was attributable to adduct formation.The specific activities of DNA samples were converted to covalentbinding indices (CBI, µmol adduct per mol DNA nucleotides/mmolchemical applied per kg animal body weight). CBI values of 25and 9 were determined for 2AAF and MeIQx in the livers of micekilled 6 h after dosing. The values were in general agreementwith the moderate carcinogenic potency of these compounds. Thespecific activities of DNA preparations obtained from the kidneys,spleens, stomachs, small intestines and large intestines ofmice treated with MeIQx and killed 6 h after dosing were 5-to 35-times less than those obtained with the liver. DNA isolatedfrom the lungs (a target organ for MeIQx tumorigenicity) ofMeIQx-treated mice was not radiolabelled at the limit of detection(CBI <0.3). With the exception of the gastrointestinal tract,the specific activities of DNA samples isolated from mice killed6 h after administration were higher than those from mice killedafter 24 h.