PROGRESSIVE DNA DAMAGE IN HEPATIC NODULES DURING 2-ACETYLAMINOFLUORENE CARCINOGENESIS

Abstract

Alkaline elution was used to detect DNA alteration in rat liver throughout the carcinogenic sequence that resulted from exposure to a standard 4-cycle feeding regimen of 2-acetylaminofluorene (AAF). At the end of 3 wk of AAF feeding, DNA from aliquots of whole liver demonstrated a small but significant degree of damage. By the end of the 4th 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 wk of AAF feeding. Two to 4 mo. following the cessation of AAF, DNA from persistent nodules was examined for evidence of alteration. Despite the prolonged absence of exposure to AAF, DNA damage had progressed and was as much as 320% greater than that seen at the end of the 1st cycle. 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.