The significance of glutathione conjugation for aflatoxin B1 metabolism in rainbow trout and coho salmon

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

“…2 Pathway of AFB 1 metabolism leading to adducts formation, cytotoxicity, genotoxicity and cancer development. metabolites, as well as in rats (Valsta et al 1988;Wogan and Newberne 1967). Also, the biliary and the urinary systems represent the major excretion routes in trout, as in catfish (Plakas 1991).…”

“…Finally, the higher efficiency of CYP-mediated AFBO production along as with the great amount of AFBO produced directly from AFB 1 and indirectly from AFL 1 might account for the high rate of DNA-adduct formation found in trout. Such results with the low GST-AFBO conjugating activity contribute to explain the extreme trout sensitivity to AFB 1 toxicity and carcinogenicity (Valsta et al 1988;Bailey et al 1996).…”

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

“…2 Pathway of AFB 1 metabolism leading to adducts formation, cytotoxicity, genotoxicity and cancer development. metabolites, as well as in rats (Valsta et al 1988;Wogan and Newberne 1967). Also, the biliary and the urinary systems represent the major excretion routes in trout, as in catfish (Plakas 1991).…”

“…Finally, the higher efficiency of CYP-mediated AFBO production along as with the great amount of AFBO produced directly from AFB 1 and indirectly from AFL 1 might account for the high rate of DNA-adduct formation found in trout. Such results with the low GST-AFBO conjugating activity contribute to explain the extreme trout sensitivity to AFB 1 toxicity and carcinogenicity (Valsta et al 1988;Bailey et al 1996).…”

Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species

“…In addition to a high rate of CYP2K1 conversion to the AFB1-exo-epoxide, there is evidence in trout of a slow rate of inactivation of the epoxide by liver GST or trapping with other nucleophiles [ 68 ]. This factor, plus the slow rate of DNA repair of bulky adducts such as the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1, in salmonids enhances the carcinogenic potency of AFB1 [ 69 , 70 ].…”

“…Conjugation of AFB1-8,9-epoxide with GSH by hepatic GSTs is a minor pathway for AFB1 metabolism in vitro and in vivo [ 68 ] and this lack of efficient detoxication is a major factor in the high sensitivity of trout to AFB1-induced HCC.…”

Inter-relationships among aflatoxin B1 (AFB1) metabolism, DNA-binding, cytotoxicity, and hepatocarcinogenesis in rainbow trout Oncorhynchus mykiss

“…Glucuronides of AFL and AFL-M1 are the major and minor biliary Phase I1 conjugates, respectively, in the untreated trout . In contrast to mammalian systems in which glutathione (GSH) conjugation of the AFB1-8,9-epoxide is a major detoxification pathway (Degen & Neumann 1978), GSH conjugation does not contribute significantly to the detoxification of AFBl in trout (Valsta et al 1988). Modification of AFB, metabolism and carcinogenesis in rainbow trout by several compounds including flavonoids, indoles, and polychlorinated biphenyls has been extensively studied in our laboratory (Bailey et al 1982, Nixon et al 1984, Dashwood et al 1988.…”

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

“…2 Pathway of AFB 1 metabolism leading to adducts formation, cytotoxicity, genotoxicity and cancer development. metabolites, as well as in rats (Valsta et al 1988;Wogan and Newberne 1967). Also, the biliary and the urinary systems represent the major excretion routes in trout, as in catfish (Plakas 1991).…”

“…Finally, the higher efficiency of CYP-mediated AFBO production along as with the great amount of AFBO produced directly from AFB 1 and indirectly from AFL 1 might account for the high rate of DNA-adduct formation found in trout. Such results with the low GST-AFBO conjugating activity contribute to explain the extreme trout sensitivity to AFB 1 toxicity and carcinogenicity (Valsta et al 1988;Bailey et al 1996).…”

Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species

“…In addition to a high rate of CYP2K1 conversion to the AFB1-exo-epoxide, there is evidence in trout of a slow rate of inactivation of the epoxide by liver GST or trapping with other nucleophiles [ 68 ]. This factor, plus the slow rate of DNA repair of bulky adducts such as the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1, in salmonids enhances the carcinogenic potency of AFB1 [ 69 , 70 ].…”

“…Conjugation of AFB1-8,9-epoxide with GSH by hepatic GSTs is a minor pathway for AFB1 metabolism in vitro and in vivo [ 68 ] and this lack of efficient detoxication is a major factor in the high sensitivity of trout to AFB1-induced HCC.…”

Inter-relationships among aflatoxin B1 (AFB1) metabolism, DNA-binding, cytotoxicity, and hepatocarcinogenesis in rainbow trout Oncorhynchus mykiss

“…Glucuronides of AFL and AFL-M1 are the major and minor biliary Phase I1 conjugates, respectively, in the untreated trout . In contrast to mammalian systems in which glutathione (GSH) conjugation of the AFB1-8,9-epoxide is a major detoxification pathway (Degen & Neumann 1978), GSH conjugation does not contribute significantly to the detoxification of AFBl in trout (Valsta et al 1988). Modification of AFB, metabolism and carcinogenesis in rainbow trout by several compounds including flavonoids, indoles, and polychlorinated biphenyls has been extensively studied in our laboratory (Bailey et al 1982, Nixon et al 1984, Dashwood et al 1988.…”

Aflatoxins in aquatic species: metabolism, toxicity and perspectives

“…2 Pathway of AFB 1 metabolism leading to adducts formation, cytotoxicity, genotoxicity and cancer development. metabolites, as well as in rats (Valsta et al 1988;Wogan and Newberne 1967). Also, the biliary and the urinary systems represent the major excretion routes in trout, as in catfish (Plakas 1991).…”

“…Finally, the higher efficiency of CYP-mediated AFBO production along as with the great amount of AFBO produced directly from AFB 1 and indirectly from AFL 1 might account for the high rate of DNA-adduct formation found in trout. Such results with the low GST-AFBO conjugating activity contribute to explain the extreme trout sensitivity to AFB 1 toxicity and carcinogenicity (Valsta et al 1988;Bailey et al 1996).…”

Species Differences in the Biotransformation of Aflatoxin B1: Primary Determinants of Relative Carcinogenic Potency in Different Animal Species

“…In addition to a high rate of CYP2K1 conversion to the AFB1-exo-epoxide, there is evidence in trout of a slow rate of inactivation of the epoxide by liver GST or trapping with other nucleophiles [ 68 ]. This factor, plus the slow rate of DNA repair of bulky adducts such as the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1, in salmonids enhances the carcinogenic potency of AFB1 [ 69 , 70 ].…”

“…Conjugation of AFB1-8,9-epoxide with GSH by hepatic GSTs is a minor pathway for AFB1 metabolism in vitro and in vivo [ 68 ] and this lack of efficient detoxication is a major factor in the high sensitivity of trout to AFB1-induced HCC.…”

Inter-relationships among aflatoxin B1 (AFB1) metabolism, DNA-binding, cytotoxicity, and hepatocarcinogenesis in rainbow trout Oncorhynchus mykiss

“…Glucuronides of AFL and AFL-M1 are the major and minor biliary Phase I1 conjugates, respectively, in the untreated trout . In contrast to mammalian systems in which glutathione (GSH) conjugation of the AFB1-8,9-epoxide is a major detoxification pathway (Degen & Neumann 1978), GSH conjugation does not contribute significantly to the detoxification of AFBl in trout (Valsta et al 1988). Modification of AFB, metabolism and carcinogenesis in rainbow trout by several compounds including flavonoids, indoles, and polychlorinated biphenyls has been extensively studied in our laboratory (Bailey et al 1982, Nixon et al 1984, Dashwood et al 1988.…”