Poirier M C, True B, Laishes B A
Cancer Res. 1982 Apr;42(4):1317-21.
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.
放射免疫分析法已用于测量喂食含0.02%或0.04% 2-乙酰氨基芴饮食的雄性Wistar-Furth大鼠肝脏和肾脏DNA中2-乙酰氨基芴的乙酰化和去乙酰化脱氧鸟苷C-8 DNA加合物。在持续喂食长达60天的过程中监测加合物形成时，1天时在肝脏中观察到大量的结合水平（80 fmol/微克DNA），到30天时达到平均230 fmol/微克DNA的最大稳态值。最初，在持续喂食期间，约80%的总C-8加合物被去乙酰化[N-脱氧鸟苷(8-基)氨基芴]，在分别给予0.04%和0.02% 2-乙酰氨基芴饮食15天和30天时，这一比例分别增加到约97%。相同动物中与肾脏DNA结合的C-8加合物水平平均为肝脏值的10%至15%，其中大于或等于80%的这些加合物为去乙酰化形式。在单独的实验中，大鼠暴露于2-乙酰氨基芴3、7、28和112天；停止含致癌物的饮食；并在喂食对照饮食的1、7和28天期间监测C-8加合物。在两种致癌物剂量下，在饮食给药3或7天后，肝脏C-8加合物迅速减少，以至于在对照饮食28天后，DNA中65%至90%的原始加合物不再存在。相比之下，在喂食0.02% 2-乙酰氨基芴28天的动物中，在对照饮食28天结束时，DNA上仍有高水平（原始C-8加合物的70%至100%)。结合2-乙酰氨基芴诱导大鼠肝脏致癌过程中发生的生物学和生化变化，讨论了这种去除C-8加合物能力的明显丧失。
