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


Buss, P; Caviezel, M; Lutz, W K (1990). Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1. Carcinogenesis, 11(12):2133-2135.

Abstract

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

Abstract

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 January 1990
Deposited On:16 Oct 2018 15:41
Last Modified:24 Sep 2019 23:41
Publisher:Oxford University Press
ISSN:0143-3334
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/carcin/11.12.2133
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093carcin11122133 (Library Catalogue)

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