In vivo covalent binding of aflatoxin metabolites isolated from animal tissue to rat-liver DNA

Jaggi, W.; Lutz, Werner; Lüthy, Jürg; Zweifel, U.; Schlatter, Ch.

doi:10.1016/0015-6264(80)90104-2

Cited by 22 publications

(4 citation statements)

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“…Results of the present study demonstrate that the pig rapidly metabolizes and clears its tissues of aflatoxins on feeding an uncontaminated diet. This adds further support to the conclusions of Jaggi et al (1980) that the risk from eating liver or meat of animals fed an aflatoxincontaminated diet are negligible. trichothecolone (3), and trichothecin (4), were isolated and characterized from anise fruits infected in fields with Trichothecium roseum van Beyma (CMI-IMI 225229).…”

Section: Discussionsupporting

confidence: 74%

“…Earlier work on in vivo covalent binding of aflatoxin metabolites led Jaggi et al (1980) to conclude that macromolecular bound aflatoxin Bx was at least 4000 times less active than B, per se with respect to binding to rat liver DNA, whereas the water-soluble conjugates were at least 100 times less potent than aflatoxin Bx itself. On this basis, they concluded that the risk to humans consuming liver or meat containing aflatoxin residues is negligible compared to that from consuming other aflatoxin-contaminated foods, such as nuts or milk.…”

Section: Discussionmentioning

confidence: 99%

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Withdrawal time required for clearance of aflatoxins from pig tissues

Furtado

Pearson

Hogberg

et al. 1982

J. Agric. Food Chem.

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The time necessary to obtain clearance of aflatoxins from the tissues of the pig after removal from a contaminated diet was determined in two trials involving 20 pigs in each. There was a significant reduction in aflatoxin levels in all organs and tissues 1 day after placing the pigs on an aflatoxin-free ration. After 2 days, only one pig contained trace amounts (<0.50 pg/kg) of aflatoxins in the tissues. Four days after removal from the contaminated diet, there were no detectable levels of aflatoxins in any of the tissues.It was also found that a naturally contaminated diet containing only 20 and 31 pg/kg aflatoxins B1 and B2, respectively, resulted in traces of aflatoxins B,, Bz, M,, and Mz in the livers and kidneys after 13-14 h withdrawal from the contaminated diet, although none were detected in any other tissues.Transmission of aflatoxins through animal products (meat, milk, and eggs) to man may result in exposure to these potent carcinogenic compounds (Armbrecht, 1971; Rodricks and Stoloff, 1977). Several research groups (Krogh et al., 1973;Murthy et al., 1975; Hayes et al., 1978; Furtado et al., 1979) have shown that aflatoxins can be deposited in the tissues of the pig, which is confirmed in a review by Stoloff (1979). Thus, meat can provide a dietary source of exposure for humans. Little is known about the length of time required for the pig to metabolize aflatoxins and, thus, clear their tissues of these contaminants.The present study was designed to determine the length of time necessary to achieve tissue clearance of aflatoxins from pigs fed a contaminated diet. This was accomplished by feeding pigs on an aflatoxin-spiked diet for 42 days and measuring the amount of these toxins and their metabolites in the tissues immediately after removal and comparing them to a similar group of animals fed an unspiked basal diet. The remaining pigs were fed a control diet and pigs from all groups were slaughtered at 1,2,4, and 8 days after being placed on this diet to ascertain the length of time necessary to obtain tissue clearance. MATERIALS AND METHODSFeeding Trials. Two feeding trials with 20 weanling crossbred pigs in each were carried out by using the same basal ration described earlier by Furtado et al. (1979). Feed and water were allowed ad libitum. The pigs were weighed weekly and feed consumption records were kept. Allotment into groups was based on sex, litter, and weight. In each trial 4 pigs were fed the control (unspiked) diet, and 16 were used to determine the time necessary for tissue clearance. In both trials, the spiked diets contained 551 and 355 pg of aflatoxins B1 and B2 per kg of feed, respectively, and the spiked and control (unspiked) rations were fed for 42 days. Then the four control pigs and four of the pigs on the experimental diet were slaughtered within 13-14 h after being taken off feed. The remaining pigs in each trial were placed on an uncontaminated control ration and fed until removed for slaughter at the selected time intervals.In trial 1, after the initial feeding period of ...

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Withdrawal time required for clearance of aflatoxins from pig tissues

Furtado

Pearson

Hogberg

et al. 1982

J. Agric. Food Chem.

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“…The macromolecular fraction containing the bound aflatoxin residues was subsequently administered to a second rat. No radioactivity was detectable on the liver DNA of the second rat (44). This means, that the binding capacity of these macromolecular metabolites is at least 4 000 times less than that of aflatoxin B1.…”

mentioning

confidence: 80%

Past and future in mycotoxin toxicology research

Schlatter

1980

Pure and Applied Chemistry

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-Before 1960 the toxicology of mycotoxins was mainly of concern to veterinarians,since outbreaks of mycotoxicoses resulted occasionally in considerable losses oflivestock. By a wider use of biotests, preferably in mammals a further decline of such intoxications probably will occur. Following the discovery of the carcinogenicity of some aflatoxins the focus turned to human health. Screening tests for carcinogenicity are still in full development. The test used most frequently is the Ames-test on microorganisms. Unfortunately many problems still must be resolved, before an extrapolation of results from these tests to man becomes possible.The examination of the carcinogenic activity of mycotoxins in long-term animal experiments is often difficult due to lack of resources, lack of test material and the toxicity of the compounds which precludes the administration of sufficiently high dose levels. The available data regarding a possible carcinogenic activity of several important mycotoxins such as the trichothecenes or patulin do not fulfil the currently used criteria.Therefore further studies are needed. A new approach is the determination of the binding capacity to DNA of suspected carcinogens, which seems to correlate well with the carcinogenic potency. By this method a high carcinogenicity of aflatoxin can be deduced, however, the macromolecular bound residues of aflatoxin B1 , which may occur in tissues of domestic animals most probably do not show a carcinogenic activity. Although many questions are still unanswered, it seems that the numerous mycotoxins identified since 1960 are less toxic or carcinogenic and occur less frequently in food than aflatoxins.Before 1960 knowledge of the toxic effects of mycotoxins originated mainly from intoxications in man and domestic animals and only occasionally were further toxicological and chemical studies subsequently initiated to elucidate the cause of the disease.

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“…This irreversibility has been confirmed in recent years by many investigations. The work of Jaggi and his co-workers (Jaggi et al 1980) on in vivo covalent binding of aflatoxin metabolites isolated from animal tissues to rat-liver DNA is a particularly good example: aflatoxin Bl has a covalent-binding index (CBI) of DNA of 10 000. This Downloaded by [New York University] at 06:44 06 August 2015…”

Section: Mechanism and Characteristics Of Covalent Bindingmentioning

confidence: 99%

Toxicological significance of covalently‐bound residues

Rico

Burgat-Sacaze

1984

Food Additives & Contaminants

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Bound residues may be defined in terms of the nonextractable radioactivity which persists in tissues after administration of radiolabelled compounds to an organism. This fraction is found to contain natural endogenous compounds resulting from incorporation of degradation products of the administered substance into intermediary metabolites (amino acids, carbohydrates etc.). However, 'new' compounds are also found which arise from covalent binding of the administered substance or its metabolites to endogenous macromolecules. The former fraction is nontoxic, but in the second case the nature of the covalent binding is important from the toxicological point of view. It is unspecific and irreversible, and often involves the action of short-lived and highly reactive intermediates. The covalent bond is usually thermodynamically irreversible. A good example is provided by bromobenzene, which binds to proteins via the 3,4-epoxide, which is the hepatotoxic agent. From the above considerations it is possible to distinguish two types of metabolites that may be found in foodstuffs prepared from drug-treated animals. The first are represented by the drug itself and its primary metabolites. These compounds are potentially more or less toxic to the consumer. The second type are the covalently bound metabolites. These have lost their reactivity in an irreversible manner and may be considered to have low toxicity to the consumer as well as low bioavailability. Some examples (trenbolone acetate, aflatoxin, carbaryl) are discussed to support this contention.

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In vivo covalent binding of aflatoxin metabolites isolated from animal tissue to rat-liver DNA

Cited by 22 publications

References 10 publications

Withdrawal time required for clearance of aflatoxins from pig tissues

Withdrawal time required for clearance of aflatoxins from pig tissues

Past and future in mycotoxin toxicology research

Toxicological significance of covalently‐bound residues

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