FORMATION AND REMOVAL OF (GUAN-8-YL)-DNA-2-ACETYLAMINOFLUORENE ADDUCTS IN LIVER AND KIDNEY OF MALE-RATS GIVEN DIETARY 2-ACETYLAMINOFLUORENE

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1317-1321
Abstract
Radioimmunoassay was used to measure acetylated and deacetylated deoxyguanosine C-8 DNA adducts of 2-acetylaminofluorene [2-AAF] 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 f[femto]mol/.mu.g DNA) were observed in liver by 1 day, and maximum steady-state values averaging 230 fmol/.mu.g DNA were reached by 30 days. Initially, during the continuous feeding, .apprx. 80% of the total C-8 adducts were deacetylated [N-deoxyguanosine(8-yl)aminofluorene], and this proportion increased to .apprx. 97% by 15 and 30 days of administration of 0.04 and 0.02% 2-AAF diets, respectively. Levels of C-8 adducts bound to kidney DNA in the same animals average 10-15% of the liver values with .gtoreq. 80% of these adducts in the deacetylated form. In separate experiments, rats were exposed to 2-AAF 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, 65-90% of the original adducts were no longer present in the DNA. In animals fed 0.02% 2-AAF for 28 days there were high levels (70-100% of the original C-8 adduct) remaining on the DNA at the end of 28 days on the 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-AAF hepatocarcinogenesis.

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