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© 1990 Oxford University Press

other

Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1

P. Buss, M. Caviezel and W.K. Lutz 2

Institue of Toxicology, Swiss Federal Institute of Technology and University of Zurich CH-8603 Schwerzenbach, Switzerland

2To whom correspondence should be addressed

Male F-344 rats were given [3H]aflatoxin B1 (AFB 1) in the drinking water at three exposure levels (0.02, 0.6, 20 µg/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 109 nucleotides, i.e. clearly proportional ot 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 turnor risk to low dose.


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