Presence of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-C8-MeIQx) in human tissues

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Abstract
One of the mutagenic and carcinogenic heterocyclic amines (HCAs), 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline (MelQx), is present in cooked foods and we are chronically exposed to this compound in our daily life. To study the role of HCAs in human carcinogenesis, we analyzed MelQx-DNA adducts in 38 DNA samples obtained from surgical and autopsy specimens by the 32 P-postlabeling method under adduct-intensification conditions with the modification of additional digestion with nuclease P1 and phosphodiesterase I after 32 P-labeling at 5′ -hydroxyl termini. This modified 32 P-postlabeling method can detect N2 -(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4, 5- f ]quinoxaline 5′-monophos-phate (5′-pdG-C8-MeIQx) at levels down to 1/10 10 nucleo-tides. The DNA samples from colon and rectum surgical specimens and a kidney taken at autopsy were found to contain an adduct spot corresponding to that of standard 5′-pdG-C8-MeIQx on TLC at levels of 14, 18 and 1.8 per 10 10 nucleotides, respectively. Each adduct spot was extracted from TLC and identified to be 5′-pdG-C8-MeIQx by HPLC. Thus, MelQx-DNA adducts actually exist in human tissues and this adduct formation may be involved in human cancer development.

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