Sterigmatocystin
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Sterigmatocystin is a polyketide
mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...
produced by certain species of ''
Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Mic ...
''. The toxin is naturally found in some cheeses. Sterigmatocystin is a toxic metabolite structurally closely related to the
aflatoxin Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly ''Aspergillus'' species. The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, sweetcorn ...
s as it is the penultimate precursor of aflatoxins B1 and G1. It contains a
xanthone Xanthone is an organic compound with the molecular formula O 6H4sub>2CO. It is a white solid. In 1939, xanthone was introduced as an insecticide and it currently finds uses as ovicide for codling moth eggs and as a larvicide. Xanthone is also ...
nucleus attached to a bifuran structure. Sterigmatocystin is mainly produced by the fungi ''
Aspergillus nidulans ''Aspergillus nidulans'' (also called ''Emericella nidulans'' when referring to its sexual form, or teleomorph) is one of many species of filamentous fungi in the phylum Ascomycota. It has been an important research organism for studying eukaryo ...
'' and '' A. versicolor''. It has been reported in mouldy grain, green coffee beans and cheese although information on its occurrence in foods is limited. It appears to occur much less frequently than the aflatoxins, although analytical methods for its determination have not been as sensitive until recently, and so it is possible that small concentrations in food commodities may not always have been detected. Although it is a potent liver carcinogen similar to
aflatoxin B1 Aflatoxin B1 is an aflatoxin produced by '' Aspergillus flavus'' and '' A. parasiticus''. It is a very potent carcinogen with a TD50 3.2 μg/kg/day in rats. This carcinogenic potency varies across species with some, such as rats and monkeys, see ...
, current knowledge suggests that it is nowhere near as widespread in its occurrence. If this is the true situation it would be justified to consider sterigmatocystin as no more than a risk to consumers in special or unusual circumstances. A number of closely related compounds such as o-methyl sterigmatocystin are known, and some may also occur naturally.


Chemical and physical properties

Sterigmatocystin forms pale yellow needles and that are readily soluble in methanol,
ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
, acetonitrile,
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
, and chloroform. Sterigmatocystin reacts with a hot solution of potassium hydroxide and ethanol and is easily methylated by methyl iodide. Treatment with ethanol in acid produces dihydroethoxysterigmatocystin.


Toxicity and importance

The toxic effects of sterigmatocystin are much the same as those of
aflatoxin B1 Aflatoxin B1 is an aflatoxin produced by '' Aspergillus flavus'' and '' A. parasiticus''. It is a very potent carcinogen with a TD50 3.2 μg/kg/day in rats. This carcinogenic potency varies across species with some, such as rats and monkeys, see ...
. It is thus considered as a potent
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
, mutagen, and teratogen. It is less acutely toxic to rodents and monkeys but appears to be slightly more toxic to
zebra fish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow Family (biology), family (Cyprinidae) of the Order (biology), order Cypriniformes. Native to South Asia, it is a popular aquarium, aquarium fish, frequently sold under ...
. The LD50 in mice is in excess of 800 mg/kg. The 10-day LD50 in Wistar rats is 166 mg/kg in males, 120 mg/kg in females, and 60–65 mg/kg for ip. administration in males. The ip. 10-day LD50 for vervet monkeys is 32 mg/kg. Chronic symptoms include induction of hepatomas in rats, pulmonary tumours in mice, renal lesions and alterations in the liver and kidneys of African Green monkeys. Rats fed 5–10 mg/kg of sterigmatocystin for two years showed a 90% incidence of liver tumours. It has been suggested that sterigmatocystin is about 1/10 as potent a carcinogen as aflatoxin B1. Toxic effects of sterigmatocystin-fed laboratory animals have included kidney and liver damage and diarrhoea. Skin and hepatic tumours are induced in rats by dermal application. Cattle exhibiting bloody diarrhoea, loss of milk production and in some cases death were found to have ingested feed containing Aspergillus versicolor and high levels of sterigmatocystin of about 8 mg/kg. The acute toxicity, carcinogenicity, and metabolism of sterigmatocystin has been compared with those for aflatoxin and several other hepatotoxic mycotoxins. The IARC-classification of sterigmatocystin is group 2B, which means it is carcinogenic in other species and is possibly
carcinogenic A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
to humans, but that a definitive link between human exposure and cancer has not been proven. Because sterigmatocystin (ST) is an intermediate of the aflatoxin biosynthesis pathway and is produced by the BSL-1 organism ''Aspergillus nidulans'', it serves as a model for studying regulation of the aflatoxin biosynthetic gene cluster (BGC). Sterigmatocystin was shown to be produced only in the absence of glucose (
carbon catabolite repression Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria and other microorganisms. Catabolite repression allows microorganisms to adapt quickly to a preferred (rapidly metabol ...
) but independent of CreA when glucose is used as sole carbon source. Instead, it was shown to be dependent on a regulator of G0 which transmits the glucose signal to downstream targets.


Natural occurrence

The occurrence of sterigmatocystin in raw materials and foods has not been reported often. The instances reported have usually been on mouldy, or poor quality materials such as wheat, maize, animal feed, hard cheese, pecan nuts and green coffee beans. While this lack of information may be due to deficiencies in the analytical methods, where surveys of good quality products have been carried out with reliable methodology, sterigmatocystin has rarely if ever been found. However, further assurance is required before sterigmatocystin can finally be dismissed as a risk because A. versicolor has been isolated frequently from cereals, grain products, fruits and marmalade, dried meat products and grapefruit juice. Relatively high levels of sterigmatocystin have been formed in bread, cured ham and salami after inoculation with A. versicolor. More than in food, sterigmatocystin is frequently found in water-damaged buildings.


Sampling and analysis

Methods for extraction of sterigmatocystin have been commonly based on a mixture of acetonitrile and 4% aqueous potassium chloride. Methods for detection using TLC are not very sensitive having a limit of detection in the range 20-50 microgrammes/kg. TLC plates must be sprayed with
aluminium chloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...
and heated. Analytical methods for the determination of sterigmatocystin have been reported using HPLC but again these are not very sensitive because of lack of UV absorbance or
fluorescence Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...
, although a post column reaction with aluminium chloride has been used to increase sensitivity. More recently, methods using HPLC linked with atmospheric pressure ionisation mass spectrometric detection have been developed for foods such as cheese, bread and corn products.


Stability and Persistence

There appear to be no reports about the stability of sterigmatocystin, other than in solution, where it is similar to the aflatoxins. There is one report that phosphine gas significantly depresses the formation of sterigmatocystin when cereals are inoculated with A. versicolor.


Legislation and control

No country has legislation for sterigmatocystin. Natural occurrence appears to be infrequent although only a limited number of surveys have been carried out. Soon after it was recognised as a highly toxic compound, the
California Department of Health Services The California Health and Human Services Agency (CHHS) is the state agency tasked with administration and oversight of "state and federal programs for health care, social services, public assistance and rehabilitation" in the U.S. state of Califor ...
used TD50 values from the Cancer Potency Database to produce ‘no significant risk’ intake levels for humans. The level resulting was 8 microgrammes/kg body weight/day for a 70 kg adult


See also

*
Dermatoxin A dermatoxin (from ''derma'', the Greek language, Greek word for skin) is a toxic chemical that damages skin, mucous membranes, or both, often leading to tissue necrosis. Dermatoxins can be drugs, natural chemicals, or synthetic chemicals. The sev ...
*
Mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...


References


External links


Chemical explanation by European Mycotoxin Awareness Network

PubChem Entry
{{Toxins Food safety IARC Group 2B carcinogens Xanthones Natural phenols Mycotoxins Aspergillus Phenol ethers