From Big Medical Encyclopedia

AFLATOXINS — group of the toxins metabolites produced by mold fungi, hl. obr. from the sort Aspergillus, possessing selective hepatotropic effect.

An event, a cut led to opening And., the outbreak of a so-called X-disease (X disease) among poultry and animals in England in 1960 was. Animals perished as a result of the acute liver failure which was followed by a necrosis and cirrhosis. A similar epizooty was observed in nurseries with an iridescent trout in California (USA) where tumors of a liver were found in 50 — 70% of fishes. The general factor connecting this epizooty was existence in a forage of animals, birds and fishes of a peanut (peanut) infected with a mold fungus of Aspergillus flavus. From extracts of the infected products the substance causing a characteristic picture of poisoning was emitted. This substance was called an aflatoxin (according to the reduced name of a fungus producer). Is later it was identified several individual connections differing on extent of hepatotoxic and gepatokantserogenny action which were designated as aflatoxins of B1, B2, G1, G1, M1, M2, V2a and G2a. Besides, it was established that And. are formed not only fungi of the sort Aspergillus, but also other mold fungi, napr, by nek-ry strains of Penicillium and Streptomyces. And. were found in a number of foodstuff — in soy, wheat, barley, corn, rice, peas, beans, in seeds of cotton and grains of cocoa, in potatoes, cheese, in powdered milk etc.

Test for existence And. in foodstuff and sterns it is offered to consider the necrotic damages of a liver defined under a microscope at ducklings.

On chemical structure And. represent the replaced coumarins about a pier. weighing 312 — 330.


They differ on saturation rate with hydrogen, and also as the deputy (R) in a furan ring (see formulas). It should be noted that available at And. the furocoumarinic configuration is characteristic of the whole group of the eurysynusic substances in the nature having pharmacological activity.

For allocation And. from the infected objects the various methods including extraction of mycotoxins the corresponding solvents are offered (methanol, chloroform, acetone — water, hexane — acetone — water etc.) with the subsequent repeated purification of extract. By means of different types of a chromatography it is possible to receive individual And., which identification is carried out on characteristic fluorescence in ultraviolet (blue-violet for And. groups B and flavovirent for And. the G) groups, on mobility in a thin coat of silica gel (the size Rf for> B1 B2>>> of G1 G2), and also on their specific absorption spectrums and fluorescence. Allocated in pure form And. represent pale yellow crystals, very poorly water soluble (10 — 20 mg/ml), but freely soluble in moderately polar organic solvents, such as chloroform, methanol, a dimethyl sulfoxide. Solutions A. are rather light-sensitive also air, however a long time (over a year) can remain in the dark and in the cold.

Strains of the fungi capable to produce And., are widespread everywhere. The majority of fungi of the sort Aspergillus develop and form And. in wide temperature limits — from 10 to 60 ° (it is especially vigorous at 23 — 30 °) in the conditions of humidity of a product more than 14%, and air — 85 — 90%. Therefore, any foodstuff and a stern can be contaminated And. at various stages of their preparation and storage. At usual ways of processing of food A., contained in it, collapse only partially. More efficient are special methods of processing: sterilization in the autoclave in the presence of ammonium or processing by hypochlorite. In the contaminated samples of foodstuff or forages the B1 fraction most often meets. The B2 and G1 fraction almost never meets for lack of B1.

Observations showed that to And. many species of mammals, birds and fishes are sensitive. Toxic action And. depends on age, sex, food and a species of an animal. On the other hand, various fractions A have various activity.

The most active is the B1 fraction, the least active — G2. So, e.g., LD 100 B1 fractions for newborn ducklings only 15 — 20 mkg, G1 fractions — 40 mkg make, B2 — 85 mkg, a G2 — 175 mkg. In pure form or as a part of pollution of groundnut meal A. have stronger toxic effect on young people, especially newborn animals. Depending on sensitivity to And. all animal species can be subdivided into three groups: 1) very sensitive for which LD50 is equal to 1000 mkg/kg of weight or less (ducklings, an iridescent trout, Guinea pigs, rabbits, newborn rats, turkey poults); 2) sensitive for which LD50 makes 1000 — 10 000 mkg/kg of weight (monkeys, calfs, chickens, hamsters, cows, etc.); 3) resistant which remain insensitive to rather high doses And. (mice and sheep).

Direct proofs of high sensitivity of the person to toxic action And. no. However it is known that cellular cultures of a liver and lungs of the person as well as cellular cultures of embryos of ducklings, are very sensitive to cytotoxic action And.

Acute intoxication And. it is characterized by slow development of necroses of a liver of various type: periportal at rats, turkey poults, chickens; tsentrilobulyarny at Guinea pigs; focal — at young monkeys. Along with necrotic changes proliferation of bilious channels is observed. Elektronnomikroskopichesky researches showed that the first changes occur in nuclear structures in 30 min. after introduction And. Later degranulation rough and proliferation of a smooth endoplasmic reticulum, disintegration of mitochondrions, increase in number of lysosomes is observed.

At chronic intoxication And. its clear gepatokantserogenny action comes to light. At various classes of animals (mammals, birds and fishes) after long introduction And. there are tumors of a liver, is more rare than kidneys, in some cases with metastasises in lungs. At the same time carcinogenic activity And. it is shown at introduction of doses many times over smaller, than during the use of such known chemical gepatokantserogen as, e.g., aminoazo compounds (see. Aminoazotoluol , Dimetilaminoazobenzol ). For receiving cancer of liver rats have enough to enter 10 mkg of an aflatoxin a day. Addition in a forage of fishes of an aflatoxin of B1 in concentration of 0,5 mkg/kg causes emergence gepaty in 40 — 50% of individuals of an iridescent trout on average in 52 weeks. 100% of rats have tumors at addition in their forage of mix A. in concentration of 700 — 800 mkg/kg. According to Nyyubern and Voganum (R. M. of Newberne, G. N.Wogan, 1967) use of the cleared aflatoxin of B1 in a dose of 15 mkg/kg causes at rats cancer of a liver with metastasises in lungs in 100% of cases within 68 — 80 weeks. Moreover, tumors of a liver can be got at rats after single introduction And. in the dose close to LD50. In experiences of in vitro A. cause malignant transformation of cells of a liver of newborn rats. On site administrations of pure crystal drugs A. under skin to rats and mice sarcomas and fibrosarcomas are formed. However and in these cases necrotic damages, and then tumors of a liver are observed at first. Comparative analysis of results of chronic introduction of separate fractions A. to rats points that the B1 fraction has the greatest activity. The dose in 100 and more times big, e.g., is necessary for induction of tumors by means of B2 fraction, than it is required for B1 fraction. Sensitivity to cancerogenic action And. raises at alimentary deficit of lipotropic factors and cirrhosis. At simultaneous introduction of Ampere-second diethylstulbestrole or phenobarbital, and also at a hypophysectomy animals become steadier against A.

Schitayetsya's action that cancerogenic action And. occurs through alkylation (see). The expressed gepatotropnost And. is explained by the fact that their most part collects in a liver, edges plays the main role in metabolism And. At the same time B1 and G1 fractions are initial toxins. Other known fractions A. — their metabolites. So, M1 and Sq.m fractions — hydroxylates of B1 fraction; they are found in urine of all animal species and the person after hit by it with food A.

Wide range of the animals sensitive to cancerogenic action And., forces to consider them potentially dangerous to the person.

During the studying of food stuffs of residents of Uganda, Thailand and Switzerland it was revealed that to 50% of samples of peanut nuts, and also and products of their processing (flour, bread) contained many grain and leguminous crops (wheat, corn, soy, haricot, coffee, cocoa) And. in concentration from 100 — 1000 mkg/kg. Therefore, And. from the contaminated products can get into a human body. In 1971. Voganum and Shank (G. N. Wogan, R. Shank) send in intercellular lymphs at the children in Thailand who died of an acute disease of an unknown etiology, significant amounts of a nemetabolizirovanny aflatoxin of B1. Pathological changes in a liver and other bodies of the dead were similar to a picture of changes in similar bodies at the monkeys poisoned with an aflatoxin of B1. In 1971 in India cases of mass cirrhosis at children in connection with accidental pollution were noted And. their food. Epidemiological researches indicate that in areas with the increased cancer cases of a liver (the Central Africa, Southeast Asia) a certain correlation with the maintenance of A is noted. in food stuffs of the population. So, in one of the districts of Uganda where incidence of primary cancer of a liver makes 15 cases on 100 thousand population, of 105 samples of foodstuff in 43,8% were found And. in concentration to 1000 mkg/kg.

To questions of studying of action And. and much attention both in our country, and in other countries, and also the international organizations UN (WHO, FAO, YuNESEF) connected with public health care and providing it with high-quality food is paid to measures of their elimination from the environment surrounding the person. In 1966 WHO experts offered a marginal dose And. in food, equal 30 mkg on 1 kg of a product.

Bibliography: Bilay V. I. Biologicheski active agents of microscopic mushrooms and their use, page 160, Kiev, 1965, bibliogr.; Bilay V. I. and Pidop-lichno of H. M. Toksinobrazuyushchiye microscopic mushrooms and diseases of the person caused by them and animals, page 106, Kiev, 1970; By and at b i of 1 1 H. F. and Shim k in M. V. Kantserogennost of forages caused by fungal metabolites or pollution of forages at their processing in book: Usp. in studying of cancer, the lane with English, under the editorship of L. M. Shabad, t. 8, page 204, M., 1969, bibliogr.; Pokrovsky A. A. and Besprozvanny B. K. Afla-toksikoza, Owls. medical, No. 2, page 79, 1972, bibliogr.; Pokrovsky A. And. ides of river. To a technique of receiving, cleaning and identification of an aflatoxin V Vopr. pitas., t. 30, No. 4, page 69, 1971, bibliogr.; Aflatoxin, scientific background, control and implication, ed. by L. A. Goldblatt, N. Y., 1969; A m 1 an I. o. Cirrhosis in children from peanut meal contaminated by aflatoxin, Amer. J. clin. Nutr., v. 24, p. 609, 1971; Barnes J.M. Aflatoxin as a health hazard, J. appl. Bact., v. 33, p. 285, 1970; Evaluation of the carcinogenic risk of chemicals to man (lARC), v. 1, p. 145, Lyon, 1972, bibliogr.; NewberneP.M.a. W o-gan G. N. Sequential morphologic changes in aflatoxin Bt carcinogenesis in the rat, Cancer Res., v. 28, p. 770, 1968; S with h o-e n t a 1 R. Aflatoxins, Ann. Rev. Pharmacol., v. 7, p. 343, 1967, bibliogr.; W o-g a n G. N. Mycotoxins in foodstuffs, Cambridge, 1964; it, Chemical nature and biological effects of the aflatoxins, Bact. Rev., v. 30, p. 460, 1966, bibliogr.; W about g a n G. N. a. S h a n k R. C. Toxicity and carcinogenicity of aflatoxins, Advanc. in environm. sei. techn., ed. by J. N. Pitts a. R. L. Metcalf, v. 2, p. 321, N. Y. a. o., 1971, bibliogr.

B. P. Bogoroditskaya; AA. E. Smetanin (pitas.), L. M. Shabad (PMC.).