Relative sensitivity of 32P-postlabelling of DNA and the autoradiographic UDS assay in the liver of mice exposed to 2-acetylaminofluorene (2AAF)

Abstract

In contrast to earlier studies conducted at lower dose levels, 2AAF is shown to induce a positive UDS response in the liver of mice dosed orally at dose levels between 500 and 1000 mg/kg. Similarly exposed mice had low levels of 2AAF-related hepatic DNA adducts at dose levels in the range 10-1000 mg/kg 2AAF, as determined by 32P-postlabelling analysis. It is concluded that the attenuated UDS response observed in the mouse liver, as compared to the rat liver, is due primarily to metabolic differences between these two species, coupled to a reduced capacity for UDS in the mouse liver for a given level of total 2AAF-related adducts per unit of DNA. These observations are compared and contrasted with identical studies conducted in the rat and reported in the preceding paper (Gallagher et al., 1991).

Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem cell–mediated liver regeneration

“…The observed differences between rats and mice could be explained by variations in the metabolism of AAF. Indeed, studies have been conducted showing differences in the effect of AAF in mice and rats in the form of adduct formation and DNA synthesis 28, 29…”

Restriction site mutation (RSM) analysis of 2-acetylaminofluorene (2-AAF)-induced mouse liver mutations and comparison with the measurement of in vivo micronucleus induction in the bone marrows of (2-AAF)-treated mice

“…2-AAF requires the involvement of the sulfotransferase enzyme in its ultimate activation, hence rats, which possesses these enzyme systems, are more sensitive to 2-AAF treatment than mice, which do not possess the sulfotransferase enzymes [9]. This species difference in 2-AAF genotoxicity is exemplified by data showing the liver UDS test was positive with 2-AAF-treated rats at 50-fold lower doses than in the case of 2-AAF-treated mice [10]. Activation of 2-AAF has also been shown to occur via the bacterial flora of the gut, which may be important in orally dosed animals [11].…”

Trends of Polycyclic Aromatic Hydrocarbon Levels and Mutagenicity in Santiago's Inhalable Airborne Particles in the Period 1992?1996

“…After the 4-h incubation the NO 2 -PAH-modified calf thymus (CT) DNA was isolated (Ashby et al, 1991;Gupta, 1994). The modified DNA samples were resuspended in 2 ml of HPLC-grade water and placed in a -80°C freezer until digestion and adduct analysis.…”