LINEAR DOSE-RESPONSE RELATIONSHIP FOR DNA ADDUCTS IN RAT-LIVER FROM CHRONIC EXPOSURE TO AFLATOXIN-B1

Male F-344 rats were given [H-3]-aflatoxin B1 (AFB1) in the drinking water at three exposure levels (0.02, 0.6, 20 mu-g/l, resulting in average dose levels of 2.2, 73, 2110 ng/kg per day). After 4, 6 and 8 weeks, DNA was isolated from the livers and analyzed for aflatoxin-DNA adducts. The level of DNA adducts did not increase significantly after 4 weeks, indicating that a steady-state for adduct formation and removal had nearly been reached. At 8 weeks, the adduct levels were 0.91, 32 and 850 nucleotide-aflatoxin adducts per 10(9) nucleotides, i.e. clearly proportional to the dose. At the high dose level, a near 50% tumor incidence would be expected in a 2-year bioassay with F-344 rats while the low dose used is within the range of estimated human dietary exposures to aflatoxin in Western countries. The proportionality seen between exposure and steady-state DNA adduct level is discussed with respect to a linear extrapolation of the tumor risk to low dose.