Susceptibility to Aflatoxin B1-Induced Carcinogenesis Correlates with Tissue-Specific Differences in DNA Repair Activity in Mouse and in Rat

Bedard, Leanne L.; Alessi, Manlio; Davey, Scott; Massey, Thomas E.

doi:10.1158/0008-5472.can-04-3373

Cited by 36 publications

(20 citation statements)

References 49 publications

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“…Not all animals are equally susceptible to carcinogenic and toxic effect of mycotoxins (26). The effects of mycotoxins are related to the amount, length of exposure, and natural sensitivity of the host to the mycotoxins (27). Glutathione-S-transferase (GST) activity may be a key factor in determining individual or species susceptibility to AFB 1 and at least in rodents is the major route of detoxification.…”

Section: Discussionmentioning

confidence: 99%

Influence of aflatoxin B1 on mRNA levels of acute-phase proteins and oncoproteins in albino rat liver

et al. 2009

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Background: The effect of aflatoxin B1 (AFB1) administration on expression of genes coding for acute-phase proteins, and nuclear protooncogenes c-fos and c-jun, and alpha-fetoprotein gene has been studied in rats. Methods: AFB1 was administered to male Albino Oxford (AO) rats as a single intraperitoneal dose (1 mg/kg body weight). The expression of genes for albumin, cystein protease inhibitor, fibrinogen, haptoglobin, a1-acid glycoprotein and for c-Fos, c-Jun and alpha-fetoprotein in rat liver was measured by Northern hybridization. Results: The mild increase in the levels of mRNA for acute-phase proteins after AFB1 administration was observed during the first 24 hours. The exceptions were the mRNA levels in liver for cystein protease inhibitor, which were 50%, decreased as compared to the control values. In addition, mild increase of the expression of c-fos protooncogene with two peaks were noted at three (1.3 fold) and 72 hours (1.5 fold) after injection AFB1 to rats. The expression of nuclear protooncogene c-jun at 1 hour and 72 hour after acute poisoning was 2.6 fold and 3.7 fold increased as compared to control values, respectively. The mRNA levels in liver for the alpha-fetoprotein reached a maximum at 1 hour after AFB1 injection and it was 1.8 times higher than the levels in the livers of nontreated animals. Conclusion: Single administration of AFB1 induced increased transcription of c-jun and c-fos genes while typical acute-phase response was not found

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Section: Discussionmentioning

confidence: 99%

Influence of aflatoxin B1 on mRNA levels of acute-phase proteins and oncoproteins in albino rat liver

et al. 2009

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“…However, the prospect remains that allyl acetate and allyl alcohol due to their greater gastrointestinal tolerability are capable of delivering higher systemic doses of acrolein through post-absorption metabolism; doses that would not be achievable through administration of acrolein itself. In tissues that may be more sensitive to mutagenesis (Bedard et al 2005) this higher rate of delivery may lead to carcinogenesis. Notably, another allyl ester, allyl isovalerate, the toxicity of which is correlated with its hydrolysis to allyl alcohol and subsequent conversion to acrolein (Butterworth et al 1975), was tested by the National Toxicology Program and was shown to be a carcinogen in male rats and female mice (1983).…”

Section: Discussionmentioning

confidence: 99%

A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein

et al. 2008

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Allyl acetate (AAC), allyl alcohol (AAL), and acrolein (ACR) are used in the manufacture of detergents, plastics, pharmaceuticals, and chemicals and as agricultural agents. A metabolic relationship exists between these chemicals in which allyl acetate is metabolized to allyl alcohol and subsequently to the highly reactive,α,β-unsaturated aldehyde, acrolein. Due to the weaker reactivity of the protoxicants, allyl acetate and allyl alcohol, relative to acrolien we hypothesized the protoxicants would attain greater systemic exposure and therefore deliver higher doses of acrolein to the internal organs. By extension, the higher systemic exposure to acrolein we hypothesized should lead to more internal organ toxicity in the allyl acetate and allyl alcohol treated animals relative to those treated with acrolein. To address our hypothesis we compared the range of toxicities produced by all three chemicals in male and female Fischer 344/N rats and B6C3F1 mice exposed 5 days a week for 3 months by gavage in 0.5% methylcellulose. Rats (10/group) were dosed with 0 to 100 mg/kg allyl acetate, 0 to 25 mg/kg allyl alcohol, or 0 to 10 mg/kg acrolein. Mice (10/group) were dosed with 0 to 125 mg/kg allyl acetate, 0 to 50 mg/kg allyl alcohol, or 0 to 20 mg/kg acrolein. The highest dose of allyl acetate and acrolein decreased survival in both mice and rats. The primary target organ for the toxicity of all three chemicals in both species and sexes was the forestomach; squamous epithelial hyperplasia was observed following exposure to each chemical. In both species the highest allyl acetate dose group exhibited forestomach epithelium necrosis and hemorrhage and the highest dose of acrolein led to glandular stomach hemorrhage. Liver histopathology was the most apparent with allyl acetate, was also observed with allyl alcohol, but was not observed with acrolein. All chemicals had effects on the hematopoietic system with allyl acetate having the most pronounced effect. When dosed at quantities limited by toxicity, allyl acetate and allyl alcohol produce higher levels of urinary mercapturic acids than the minimally toxic dose of acrolein. This observation is likely due to biotransformation of allyl acetate and ally alcohol to acrolein that occurs after absorption and suggests that these chemicals are protoxicants that increase systemic exposure of acrolein. Increased systemic exposure to acrolein is likely responsible for the differences in hepatic toxicological profile observed with these chemicals.

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“…For example, in rodents it has been recently discovered that species-and tissue-related differences in DNA damage recognition and repair well correlated with species susceptibility to AFB 1 -induced carcinogenesis. Bedard et al (2005) demonstrated that mouse liver exhibited a repair activity towards AFB 1 -N7-Gua and AFB 1 -FAPY, which was 6-fold and 4-fold higher than those of rat liver, respectively. However, mouse liver repaired AFB 1 -FAPY less effectively than AFB 1 -N7-Gua, suggesting that DNA repair efficiency depends on the type of DNA lesions.…”

Section: Mutagenicitymentioning

confidence: 95%

“…However, mouse liver repaired AFB 1 -FAPY less effectively than AFB 1 -N7-Gua, suggesting that DNA repair efficiency depends on the type of DNA lesions. (Bedard et al 2005). In fact AFB 1 -FAPY, because of its slow removal from DNA, was found to be implicated in the initiation of liver carcinoma (Croy and Wogan, 1981).…”

Section: Mutagenicitymentioning

confidence: 99%

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

Santacroce

Conversano

Casalino

et al. 2007

Rev Fish Biol Fisheries

159

119

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Among all known mycotoxins, aflatoxins represent the most investigated, widespread and worrisome source of contamination of foods and feed worldwide. In the early 1960s, soon after the finding of aflatoxin B 1 (AFB 1 ) in the feedstuffs of aquacultured rainbow trout that had died in an epizootic of hepatomas, great scientific discoveries were made in several areas by a number of researchers under the direction of scientists like J. Halver, R. 0. Sinnhuber, G. S. Bailey, J. D. Hendricks and colleagues. Since that time, several studies have focused on the identification of new isoenzymes involved in AFB 1 metabolism and on the discovery of new modulators in AFB 1 -induced cancer initiation and progression. However, metabolic and toxicological studies on aflatoxins in marine aquacultured species are fragmented and restricted to a limited number of fish species. Aflatoxins exert a substantial impact on the fish farming production, causing disease with high mortality and a gradual decline of reared fish stock quality, thus representing a significant problem in aquaculture systems. Based on these considerations, the goals of this review article are: (1) to gather the currently available scientific information, summarising existing data on aflatoxin contamination on feeds and fishmeals, and toxicological effects induced in reared aquatic species; (2) to make a comparative analysis of AFB 1 metabolism in the most representative species studied; (3) to gain new insights on the risk of DNA damage caused by aflatoxins on fish genomes and their role in cancer development.

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Susceptibility to Aflatoxin B1-Induced Carcinogenesis Correlates with Tissue-Specific Differences in DNA Repair Activity in Mouse and in Rat

Cited by 36 publications

References 49 publications

Influence of aflatoxin B1 on mRNA levels of acute-phase proteins and oncoproteins in albino rat liver

Influence of aflatoxin B1 on mRNA levels of acute-phase proteins and oncoproteins in albino rat liver

A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

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