Use of monkey liver microsomes in production of aflatoxin Q1

Dp, Hsieh; Ji, Dalezios; Ri, Krieger; Ms, Masri; Wf, Haddon

doi:10.1021/jf60193a048

Cited by 24 publications

(6 citation statements)

References 7 publications

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“…AFM1, AFQ1, and AFH1 were prepared by biotransformation of AFB1 using monkey liver homogenates (14,17). AFL was prepared by a similar biotransformation method to be published elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…Among these metabolites, aflatoxins Q, (AFQ1), M1 (AFM1), Bk (AFBa), and P1 (AFP1), aflatoxicol (AFL), and aflatoxicol H1 (AFLH1) ( Table 1) are the biotransformation products of AFB1 when the latter is incubated with liver preparations and a NADPH-generating system (13)(14)(15)(16)(17). Since evidence has indicated that AFB1 requires metabolic activation for its toxic, mutagenic, and/or carcinogenic activity (18)(19)(20)(21)(22), the toxicity of each metabolite has been of great interest in the search for the active molecular species.…”

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confidence: 99%

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Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Wong¹,

Hsieh²

1976

Proc. Natl. Acad. Sci. U.S.A.

221

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Aflatoxins and their animal biotransformation products were screened for carcinogenic potential using the Ames' in vitro microbial detection system for carcinogens as bacterial mutagens [B. N. Ames et aL (1973) Proc (1). The four naturally occurring AFs, aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2), when administered as mixtures, were a potent class of animal hepatocarcinogens (2-6). They have been also associated with neoplastic formations in tissues and organs other than the liver (3,(6)(7)(8)(9).Tests with rats (10) and rainbow trout (11) have revealed that AFB1 is a potent hepatocarcinogen; AFG1 is also considerably carcinogenic, but AFB2 and AFG2 possess much lower activity. Recent studies on the metabolism of AFB1 have resulted in the isolation and identification of numerous metabolites, all of minor structural variations but significantly different biological activity relative to the parent compound (12).Among these metabolites, aflatoxins Q, (AFQ1), M1 (AFM1), Bk (AFBa), and P1 (AFP1), aflatoxicol (AFL), and aflatoxicol H1 (AFLH1) (Table 1) are the biotransformation products of AFB1 when the latter is incubated with liver preparations and a NADPH-generating system (13-17). Since evidence has indicated that AFB1 requires metabolic activation for its toxic, mutagenic, and/or carcinogenic activity (18)(19)(20)(21)(22), the toxicity of each metabolite has been of great interest in the search for the active molecular species. Attempts have been made to correlate the relative activity of the different metabolic pathways and the variations in the species susceptibility to aflatoxicosis (16,23 (24,25). The analysis of the known major AF metabolites in our study permits an observation of the structureactivity relationships as related to the carcinogenic potential of the AFs. MATERIALS AND METHODSChemicals are obtained as follows: AFBI, AFG1, AFB2, and AFG2 were purchased from Makor Chemicals, Ltd., Jerusalem, Israel. AFM1, AFQ1, and AFH1 were prepared by biotransformation of AFB1 using monkey liver homogenates (14, 17). AFL was prepared by a similar biotransformation method to be published elsewhere. AFB2k and AFGk were chemically synthesized from AFB1 with dilute acid (27). AFP1 was a chemically synthesized product kindly provided by G. N. Wogan, Massachusetts Institute of Technology, Cambridge, Mass. The purity and identity of all AFs was checked by fluorodensitometric analysis of thin-layer chromatography plates and mass spectrometry. In addition, AFQ1, AFM1, AFH1, and AFB2k were checked by high-pressure liquid chromatography (28). All biochemicals, NADP+, glucose 6-phosphate, histidine, and biotin, were purchased from Sigma Chemicals, St. Louis, Mo.The bacterial tester strain, Salmonella typhimurium strain TA 98 (21), was the generous gift of B. N. Ames, University of California, Berkeley. The bacteria were stored and grown as outlined by McCann et al. (21). The hepatic S-9 enzyme preparation was prepared from Charles River male white rats (200-250 g) and utilized according to procedur...

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“…AFM1, AFQ1, and AFH1 were prepared by biotransformation of AFB1 using monkey liver homogenates (14,17). AFL was prepared by a similar biotransformation method to be published elsewhere.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Wong¹,

Hsieh²

1976

Proc. Natl. Acad. Sci. U.S.A.

221

View full text Add to dashboard Cite

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“…There is a need for a sensitive analytical method for the quantification of small quantities of AFQI. Thin-layer chromatography and highpressure liquid chromatography are most commonly used for the analysis of AFQ1 and other aflatoxins at present (3,8,14,15,17,22,23,31). Although high-pressure liquid chromatography is sensitive, instrumentation is costly; it requires extensive cleanup for the samples to be analyzed, and only single samples can be analyzed at one time.…”

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confidence: 99%

Production and characterization of antibody against aflatoxin Q1

Fan¹,

Zhang²,

Chu³

1984

Appl Environ Microbiol

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Antibodies against aflatoxin Q1 (AFQ,) were obtained from rabbits after immunization of either AFQ1hemisuccinate or AFQ2a conjugated to bovine serum albumin. Both radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) were used for the determination of antibody titers and specificities. Antibodies obtained from rabbits after immunization with AFQ1-hemisuccinate-bovine serum albumin had the highest affinity to aflatoxin B1, whereas antibodies obtained from rabbits after immunization with AFQ2a-bovine serum albumin bound most effectively with AFQ2a. AFQ2a antibody was selected for the subsequent direct and indirect ELISA for the detection of AFQ1 in biological fluids. When AFQ2aperoxidase and AFQ2a antibody were used, direct ELISA was able to detect as low as 2 ppb (ng/ml) of AFQ1 spiked in the urine samples that had been subjected to a Sep-Pak cleanup treatment. In indirect ELISA in which the antigen (AFQ2a-bovine serum albumin) was coated to the solid phase followed by reaction with rabbit antibody and goat anti-rabbit immunoglobulin G-peroxidase conjugate, 50-fold less antibody was used without sacrificing sensitivity. Recoveries of AFQ1 added to urine samples (2 to 40 ppb) were 46.3 to 73% and 65.8 to 85.8% for direct and indirect ELISA, respectively.

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“…AFB, was purified by repeated thin-layer chromatography (TLC) on silica gel (Brinkmann Instruments Inc., Westbury, N.Y.), followed by high-pressure liquid chromatography (8). Standard AFB, and its metabolites AFL, AFP,, AFQ,, AFM,, and AFB, were prepared as previously described (7,13).…”

mentioning

confidence: 99%