Mouse liver glutathione S-transferase isoenzyme activity toward aflatoxin B1-8,9-epoxide and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide

Ramsdell, Howard S.; Eaton, David L.

doi:10.1016/0041-008x(90)90183-u

Cited by 50 publications

(17 citation statements)

References 22 publications

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“…The high activity displayed by constitutive mouse Yc GST, compared to rat, is thought to be the major factor for the remarkable resistance of mice (98,(117)(118)(119)(120)(121). The importance of this enhanced phase II reaction is confirmed by the observation that mice are actually more prolific at production of AFBI-8,9-epoxide than rats.…”

Section: Cytochromes P450supporting

confidence: 61%

Fish models for environmental carcinogenesis: the rainbow trout.

Bailey

Williams

Hendricks

1996

Environ Health Perspect

171

114

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Progress over the past 30 years has revealed many strengths of the rainbow trout as an alternative model for environmental carcinogenesis research. These include low rearing costs, an early life-stage ultrasensitive bioassay, sensitivity to many classes of carcinogen, a well-described tumor pathology, responsiveness to tumor promoters and inhibitors, and a mechanistically informative nonmammalian comparative status. Low-cost husbandry, for example, has permitted statistically challenging tumor study designs with up to 10,000 trout to investigate the quantitative interrelationships among carcinogen dose, anticarcinogen dose, DNA adduct formation, and final tumor outcome. The basic elements of the trout carcinogen bioassay include multiple exposure routes, carcinogen response, husbandry requirements, and pathology. The principal known neoplasms occur in liver (mixed hepatocellular/cholangiocellular adenoma and carcinoma, hepatocellular carcinoma), kidney (nephroblastoma), swim bladder (adenopapilloma), and stomach (adenopapilloma). Trout possess a complex but incompletely characterized array of cytochromes P450, transferases, and other enzymic systems for phase and phase 11 procarcinogen metabolism. In general, trout exhibit only limited capacity for DNA repair, especially for removal of bulky DNA adducts. This factor, together with a high capacity for P450 bioactivation and negligible glutathione transferase-mediated detoxication of the epoxide, accounts for the exceptional sensitivity of trout to aflatoxin B1 carcinogenesis. At the gene level, all trout tumors except nephroblastoma exhibit variable and often high incidences of oncogenic Ki-ras gene mutations. Mutations in the trout p53 tumor suppressor gene have yet to be described. There are many aspects of the trout model, especially the lack of complete organ homology, that limit its application as a surrogate for human cancer research. Within these limitations, however, it is apparent that trout and other fish models can serve as highly useful adjuncts to conventional rodent models in the study of environmental carcinogenesis and its modulation. For some problems, fish models can provide wholly unique approaches.Environ Health Perspect 104(Suppl 1): 5-21 (1996)

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Section: Cytochromes P450supporting

confidence: 61%

Fish models for environmental carcinogenesis: the rainbow trout.

Bailey

Williams

Hendricks

1996

Environ Health Perspect

171

114

View full text Add to dashboard Cite

show abstract

“…Among its various activities, GST plays an important role in protecting cells from reactive epoxides [85]. This is believed to occur via the catalytic addition of GSH to the epoxide moiety, as observed by the metabolism of aflatoxin B1 to an 8,9-epoxide which is detoxified by GST [86]. GST is the predominant enzyme found in ovarian carcinoma and several studies have been performed to determine whether levels of this enzyme have prognostic significance, where the levels of GSTs were correlated to a poor response to chemotherapy.…”

Section: Glutathione-s-transferease (Gst)mentioning

confidence: 99%

Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

Eid¹,

El-Readi²,

Fatani³

et al. 2015

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“…The oxidation activity toward AFB 1 was determined by HPLC using conditions that we have described previously [Yip and Coulombe, 2006], which were optimized in preliminary experiments. Because of its short half-life, AFBO was indirectly measured as the glutathione (GSH)-trapped conjugate, which provides an accurate and quantitative measurement [Ramsdell and Eaton, 1990]. E. coli membranes expressing tP4503A37 (0.307 M ), BHA-induced mouse cytosol ( ϳ 800 g) as a source of glutathione Stransferase (GST), and 2-250 M AFB 1 were added to the assay mixture as substrate.…”

Section: Analysis Of Biological Activitymentioning

confidence: 99%

Structure, Genetic Mapping, and Function of the Cytochrome P450 3A37 Gene in the Turkey <i>(Meleagris gallopavo)</i>

Rawal

Mendoza

Reed

et al. 2009

Cytogenet Genome Res

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Cytochromes P450 (P450 for protein; CYP for gene) are a superfamily of membrane-bound hemoproteins that oxidize a large number of endogenous and exogenous compounds. Through oxidation reactions, these enzymes are often responsible for the toxic and carcinogenic effects of natural food-borne toxicants, such as the mycotoxin aflatoxin B₁ (AFB₁). Previous studies in our laboratory have shown that the extreme sensitivity of turkeys to AFB₁ is in part explained by efficient hepatic P450-mediated epoxidation to the toxic and reactive metabolite the exo-AFB₁-8,9-epoxide (AFBO). Using 3′-5′-rapid amplification of cDNA ends (RACE), we amplified CYP3A37 from turkey liver RNA, the E. coli-expressed protein which efficiently epoxidates AFB₁. Turkey CYP3A37 has an ORF of 1512 bp, and the protein is predicted to be 504 amino acids with 97% homology to chicken CYP3A37. The turkey gene is organized into 13 exons and 12 introns. A single nucleotide polymorphism in the 11th intron was used to assign CYP3A37 to turkey linkage group 10 (corresponding to chicken chromosome 14, GGA14). Because of the important role of P450s in the extreme sensitivity of turkeys to the toxic effects of AFB₁, this study will contribute to the identifying allelic variants of this important gene in poultry.

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Mouse liver glutathione S-transferase isoenzyme activity toward aflatoxin B1-8,9-epoxide and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide

Cited by 50 publications

References 22 publications

Fish models for environmental carcinogenesis: the rainbow trout.

Fish models for environmental carcinogenesis: the rainbow trout.

Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

Structure, Genetic Mapping, and Function of the Cytochrome P450 3A37 Gene in the Turkey <i>(Meleagris gallopavo)</i>

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