Biomaterial Database

Metabolism of fusarin C by rat liver microsomes. Role of esterase and cytochrome P-450 enzymes with respect to the mutagenicity of fusarin C in Salmonella typhimurium. 1989

S J Lu, and M H Li, and S S Park, and H V Gelboin, and A M Jeffrey

Department of Chemical Etiology and Carcinogenesis, Chinese Academy of Medical Sciences, Beijing.

Fusarin C (FC) is a potent mutagen present on Fusarium moniliforme contaminated corn. This compound requires metabolic activation for which microsomes from phenobarbital-induced rats are most effective. Inhibition of the simultaneously induced esterase activity, which produced a less mutagenic metabolite, doubled the mutagenicity of FC. Carbon monoxide inhibited the mutagenicity of FC, suggesting the involvement of a heme containing enzyme. However, monoclonal antibodies specific for the phenobarbital-induced cytochrome P-450 enzymes PB-4 and PB-5, while inhibiting O-demethylation of p-nitroanisole and aflatoxin B1 mutagenicity, had not effect on FC mutagenicity. This implies that either these enzymes are not involved in the activation of FC or FC competes well with the antibodies for binding to the cytochrome P-450 enzymes. Two additional metabolites of FC were detected. One had an ultraviolet spectrum similar to FC: the other had a lambda max at 326 nm, and its retention time on reverse phase HPLC was very sensitive to changes in pH.

UI	MeSH Term	Description	Entries
D007531	Isoflurophate	A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.	DFP,Diisopropylfluorophosphate,Fluostigmine,Bis(1-methylethyl) Phosphorofluoridate,Di-isopropylphosphorofluoridate,Diisopropylphosphofluoridate,Dyflos,Floropryl,Fluorostigmine,Di isopropylphosphorofluoridate
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009152	Mutagenicity Tests	Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.	Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011090	Polyenes	Hydrocarbons with more than one double bond. They are a reduced form of POLYYNES.	Cumulenes
D002248	Carbon Monoxide	Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)	Monoxide, Carbon
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004950	Esterases	Any member of the class of enzymes that catalyze the cleavage of an ester bond and result in the addition of water to the resulting molecules.	Esterase
D000348	Aflatoxins	Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2.	Aflatoxin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia