PRESENCE OF 2-(DEOXYGUANOSIN-8-YL)-2-AMINO-3,8-DEMETHYLIMIDAZO [4,5-F]QUINOXALINE (DG-C8-MEIQX) IN HUMAN TISSUES

One of the mutagenic and carcinogenic heterocyclic amines (HCAs), 2-am ino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), is present in cooke d foods and we are chronically exposed to this compound in our daily l ife, To study the role of HCAs in human carcinogenesis, we analyzed Me IQx-DNA adducts in 38 DNA samples obtained from surgical and autopsy s pecimens by the P-32-postlabeling method under adduct-intensification conditions with the modification of additional digestion with nuclease P1 and phosphodiesterase I after P-32-labeling at 5'-hydroxyl termini . This modified P-32-postlabeling method can detect -yl)-2-amino-3,8-d imethylimidazo[4,5-f]quinoxaline 5'-monophosphate (5'-pdG-C8-MeIQx) at levels down to 1/10(10) nucleotides, The DNA samples from colon and r ectum surgical specimens and a kidney taken at autopsy were found to c ontain an adduct spot corresponding to that of standard 5'-pdG-C8-MeIQ x on TLC at levels of 14, 18 and 1.8 per 10(10) nucleotides, respectiv ely, Each adduct spot was extracted from TLC and identified to be 5'-p dG-C8-MeIQx by HPLC. Thus, MeIQx-DNA adducts actually exist in human t issues and this adduct formation may be involved in human cancer devel opment.