Sterigmatocystin
Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.
Sterigmatocystin is a toxic metabolite structurally closely related to the aflatoxins as it is the penultimate precursor of aflatoxins B1 and G1. It contains a xanthone nucleus attached to a bifuran structure. Sterigmatocystin is mainly produced by the fungi Aspergillus nidulans 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, 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, 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, acetonitrile, benzene, 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. It is thus considered as a potent carcinogen, mutagen, and teratogen. It is less acutely toxic to rodents and monkeys but appears to be slightly more toxic to zebra fish. 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 to humans, but that a definitive link between human exposure and cancer has not been proven.
Because sterigmatocystin 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. Sterigmatocystin was shown to be produced only in the absence of glucose 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.