Formation and removal of (guan-8-yl)-DNA-2-acetylaminofluorene adducts in liver and kidney of male rats given dietary 2-acetylaminofluorene.

Radioimmunoassay has been used to measure acetylated and deacetylated deoxyguanosine C-8 DNA adducts of 2-acetylaminofluorene in liver and kidney DNA of male Wistar-Furth rats fed a dietary regimen of 0.02 or 0.04% 2-acetylaminofluorene. When adduct formation was monitored during continuous feeding up to 60 days, substantial levels of binding (80 fmol/microgram DNA) were observed in liver by 1 day, and maximum steady-state values averaging 230 fmol/microgram DNA were reached by 30 days. Initially, during the continuous feeding, about 80% of the total C-8 adducts were deacetylated [N-deoxyguanosin(8-yl)aminofluorene], and this proportion increased to about 97% by 15 and 30 days of administration of 0.04 and 0.02% 2-acetylaminofluorene diets, respectively. Levels of C-8 adducts bound to kidney DNA in the same animals averaged 10 to 15% of the liver values with greater than or equal to 80% of these adducts in the deacetylated form. In separate experiments, rats were exposed to 2-acetylaminofluorene for 3, 7, 28, and 112 days; the carcinogen-containing diet was discontinued; and C-8 adducts were monitored during 1, 7, and 28 days of feeding control diet. At both carcinogen doses, after dietary administration for 3 or 7 days, there was a rapid decrease in liver C-8 adducts so that, after 28 days on control diet, 65 to 90% of the original adducts were no longer present in the DNA. In contrast, in animals fed 0.02% 2-acetylaminofluorene for 28 days, there were high levels (70 to 100% of the original C-8 adduct) remaining on the DNA at the end of 28 days on control diet. This apparent loss in capacity for removal of C-8 adducts is discussed in relation to biological and biochemical changes induced in the rat liver during 2-acetylaminofluorene hepatocarcinogens.