Age-related induction and disappearance of carcinogen-DNA-adducts in livers of rats exposed to low levels of 2-acetylaminofluorene.
It was investigated whether in vivo aging of rat liver is associated with changes in the induction and rate of disappearance of DNA damage. For this purpose 6- and 36-month-old rats were intraperitoneally injected with a single, low dose (5 mg/kg body wt.) of the model liver carcinogen 2-acetylaminofluorene (AAF). Using the 32P-postlabeling assay we found that N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) was the major DNA-adduct formed. The minor adduct N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-C8-AAF) could only be detected after doses of 20 mg/kg or more. Quantitation of adduct levels at various time points after treatment indicated a rapid induction of AF-adducts, which were already present at 6 h after treatment. The subsequent loss of AF-adducts was relatively slow, as was indicated by the presence of a substantial amount of AF-adducts as late as 21 days after treatment. Slight age-related differences in the pattern of induction and disappearance of AF-adducts and a somewhat higher level of persisting lesions in old than in young rats were observed.
Mullaart
E
E
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Boerrigter
M E
ME
Lohman
P H
PH
Vijg
J
J
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000375:Aging; D000818:Animals; D002850:Chromatography, Gel / Q000379:methods; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000254:growth & development* / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains
D010761:Phosphorus Radioisotopes; D004247:DNA; D015073:2-Acetylaminofluorene