Progressive DNA damage in hepatic nodules during 2-acetylaminofluorene carcinogenesis.

The method of alkaline elution was used to detect DNA alteration in rat liver throughout the carcinogenic sequence that resulted from exposure to a standard four-cycle feeding regimen of 2-acetylaminofluorene (AFF). At the end of 3 weeks of AAF feeding, DNA from aliquots of whole liver demonstrated a small but significant degree of damage. By the end of the fourth AAF feeding, the liver exhibited numerous nodules that could be dissected free from surrounding tissue. DNA from these putative premalignant lesions showed approximately 136% more damage than that seen at the end of 3 weeks of AAF feeding. Two to 4 months following the cessation of AAF, DNA from persistent nodules was examined for eivdence of alteration. Despite the prolonged absence of exposure to AAF, DNA damage was found to have progressed and was as much as 320% greater than that seen at the end of the first cycle. While the persistence of DNA damage during chronic exposure to a carcinogen has been reported previously, the observations that the DNA of a focal lesion which is putatively premalignant was damaged and, further, that this alteration progressed in the absence of a carcinogen, are unique.