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

Carcinogenesis. 1990 Dec;11(12):2133-5. doi: 10.1093/carcin/11.12.2133.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aflatoxin B1
  • Aflatoxins / pharmacology*
  • Animals
  • Carcinogens / pharmacology*
  • DNA / drug effects*
  • DNA / metabolism
  • DNA Repair / drug effects
  • Dose-Response Relationship, Drug
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Inbred F344

Substances

  • Aflatoxins
  • Carcinogens
  • DNA
  • Aflatoxin B1