Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1.
Male F-344 rats were given [3H]aflatoxin B1 (AFB1) in the drinking water at three exposure levels (0.02, 0.6, 20 micrograms/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.
Buss
P
P
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Caviezel
M
M
Lutz
W K
WK
D000284:Administration, Oral; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000348:Aflatoxins; D002273:Carcinogens; D004247:DNA; D016604:Aflatoxin B1